2024-03-28T13:13:25Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/86172019-08-30T11:32:39Zcom_10033_6804com_10033_6799col_10033_6883
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2003-08-01
The EMBO Journal 2003 22(15):4003-4013
0261-4189
1460-2075
12881434
10.1093/emboj/cdg367
http://hdl.handle.net/10033/8617
169040
en_US
Oxford University Press
http://www.emboj.oupjournals.org/content/vol22/issue15/
Copyright © 2003 European Molecular Biology Organization
Telomere shortening impairs organ regeneration by inhibiting cell cycle re-entry of a subpopulation of cells
YES
2018-06-13T04:15:47Z
ORIGINAL
satyanarayana et al_final.pdf
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Extracted Text
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2019-08-30 11:32:39.496
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
oai:repository.helmholtz-hzi.de:10033/86672019-08-30T11:27:08Zcom_10033_6804com_10033_6799col_10033_6883
Satyanarayana, A.
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Schaetzlein, S.
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Molecular and Cellular Biology 2004 24(12):5459-5474
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419883
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American Society for Microbiology
Copyright © 2004, American Society for Microbiology
Mitogen Stimulation Cooperates with Telomere Shortening To Activate DNA Damage Responses and Senescence Signaling
YES
2018-06-12T22:59:36Z
ORIGINAL
Satyanarayana et al_final.pdf
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Open Access publication
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Satyanarayana et al_final.pdf.txt
Satyanarayana et al_final.pdf.txt
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THUMBNAIL
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2019-08-30 11:27:08.563
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
oai:repository.helmholtz-hzi.de:10033/86972019-08-30T11:24:27Zcom_10033_6804com_10033_6799col_10033_6883
Kossatz, Uta
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Dietrich, Nils
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Zender, Lars
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Buer, Jan
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Manns, Michael P
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Malek, Nisar P.
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2007-02-21T08:37:01Z
2004-11-01
2007-02-21T08:37:01Z
2004-11-01
Genes & Development 2004 18(21):2602-2607
0890-9369
15520280
10.1101/gad.321004
http://hdl.handle.net/10033/8697
525540
en_US
Cold Spring Harbor Laboratory Press
Copyright © 2004, Cold Spring Harbor Laboratory Press
Skp2-dependent degradation of p27kip1 is essential for cell cycle progression
YES
2018-06-13T09:28:27Z
ORIGINAL
Kossatz et al_final.pdf
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free text from PubMed Repository
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true
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Kossatz et al_final.pdf.txt
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THUMBNAIL
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2019-08-30 11:24:27.343
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
oai:repository.helmholtz-hzi.de:10033/87052019-08-30T11:25:07Zcom_10033_6804com_10033_6799col_10033_6883
Blumenthal, Antje
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Lauber, Jörg
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Hoffmann, Reinhard
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Ernst, Martin
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Keller, Christine
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Buer, Jan
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Ehlers, Stefan
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Reiling, Norbert
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2007-02-21T08:45:00Z
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Infection and Immunity 2005 73(6):3330-3341
0019-9567
1098-5522
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10.1128/IAI.73.6.3330-3341.2005
http://hdl.handle.net/10033/8705
1111816
en_US
American Society for Microbiology
Copyright © 2005, American Society for Microbiology
Common and Unique Gene Expression Signatures of Human Macrophages in Response to Four Strains of Mycobacterium avium That Differ in Their Growth and Persistence Characteristics
YES
2018-06-12T17:37:07Z
ORIGINAL
Blumenthal et al_final.pdf
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free text from PMC repository
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Blumenthal et al_final.pdf.txt
Blumenthal et al_final.pdf.txt
Extracted Text
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THUMBNAIL
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Generated Thumbnail
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2019-08-30 11:25:07.782
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
oai:repository.helmholtz-hzi.de:10033/123682019-08-30T11:37:00Zcom_10033_6804com_10033_6799col_10033_6883
Franzke, Anke
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500
Geffers, Robert
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Hunger, J Katrin
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Pförtner, Susanne
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Piao, Wenji
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Ivanyi, Philipp
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Grosse, Jens
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Probst-Kepper, Michael
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Ganser, Arnold
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Buer, Jan
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2007-06-14T12:13:49Z
2007-06-14T12:13:49Z
2006
BMC Genomics 2006, 7:263
1471-2164
17052335
10.1186/1471-2164-7-263
http://hdl.handle.net/10033/12368
BACKGROUND: Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular immune response. To overcome this technical problem we performed a microarray analysis of CD3+ T-cells derived from bone marrow aspirates and peripheral blood samples of newly diagnosed AA patients and healthy volunteers. Two AA patients were additionally analyzed after achieving a partial remission following immunosuppression. The regulation of selected candidate genes was confirmed by real-time RT-PCR. RESULTS: Among more than 22,200 transcripts, 583 genes were differentially expressed in the bone marrow of AA patients compared to healthy controls. Dysregulated genes are involved in T-cell mediated cytotoxicity, immune response of Th1 differentiated T-cells, and major regulators of immune function. In hematological remission the expression levels of several candidate genes tend to normalize, such as immune regulators and genes involved in proinflammatory immune response. CONCLUSION: Our study suggests a pivotal role of Th1/Tc1 differentiated T-cells in immune-mediated marrow destruction of AA patients. Most importantly, immune regulatory genes could be identified, which are likely involved in the recovery of hematopoiesis and may help to design new therapeutic strategies in bone marrow failure syndromes.
-1 bytes
application/pdf
YES
en
Identification of novel regulators in T-cell differentiation of aplastic anemia patients.
Article
2018-06-12T22:34:51Z
BACKGROUND: Aplastic anemia (AA) is a bone marrow failure syndrome mostly characterized by an immune-mediated destruction of marrow hematopoietic progenitor/stem cells. The resulting hypocellularity limits a detailed analysis of the cellular immune response. To overcome this technical problem we performed a microarray analysis of CD3+ T-cells derived from bone marrow aspirates and peripheral blood samples of newly diagnosed AA patients and healthy volunteers. Two AA patients were additionally analyzed after achieving a partial remission following immunosuppression. The regulation of selected candidate genes was confirmed by real-time RT-PCR. RESULTS: Among more than 22,200 transcripts, 583 genes were differentially expressed in the bone marrow of AA patients compared to healthy controls. Dysregulated genes are involved in T-cell mediated cytotoxicity, immune response of Th1 differentiated T-cells, and major regulators of immune function. In hematological remission the expression levels of several candidate genes tend to normalize, such as immune regulators and genes involved in proinflammatory immune response. CONCLUSION: Our study suggests a pivotal role of Th1/Tc1 differentiated T-cells in immune-mediated marrow destruction of AA patients. Most importantly, immune regulatory genes could be identified, which are likely involved in the recovery of hematopoiesis and may help to design new therapeutic strategies in bone marrow failure syndromes.
ORIGINAL
Franzke_BMC Genomics_fin.pdf
Franzke_BMC Genomics_fin.pdf
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LICENSE
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false
TEXT
Franzke_BMC Genomics_fin.pdf.txt
Franzke_BMC Genomics_fin.pdf.txt
Extracted Text
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THUMBNAIL
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oai:hzi.openrepository.com:10033/12368
2019-08-30 11:37:00.093
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/128582019-08-30T11:24:31Zcom_10033_6804com_10033_6799col_10033_6883
Becker, Christian
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500
Lienenklaus, Stefan
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Jablonska, Jadwiga
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Bauer, Heike
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Weiss, Siegfried
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2007-07-23T11:38:53Z
2007-07-23T11:38:53Z
2007-01-01
J. Mol. Med. 2007, 85(1):63-73
0946-2716
17109130
10.1007/s00109-006-0107-8
http://hdl.handle.net/10033/12858
Interferon-gamma (IFN-gamma) is considered a key cytokine involved in the preventive and defensive responses of T cells against infectious pathogens and tumors. Therefore, the transgenic expression of IFN-gamma in specific T cells appears to be an obvious therapeutic possibility. To directly examine whether IFN-gamma production can be increased in T cells, we introduced an IFN-gamma encoding cDNA into IFN-gamma(-/-) and IFN-gamma(+/+) CD8(+) effector populations by retroviral transduction. Here, we show that CD8 T cells can be equipped with IFN-gamma that increases their capacity to secrete the cytokine. Despite constitutive retroviral IFN-gamma mRNA transcription, translation and secretion of IFN-gamma protein was tightly regulated and only observed in activated T cells. Neither proliferation nor cytolytic activity of CTL was affected by IFN-gamma transduction. Importantly, CD8(+) T cells retrovirally transduced with IFN-gamma exhibit augmented tumor suppressive capacity upon adoptive transfer into IFN-gamma(-/-) mice. Thus, T cells can be readily armed with IFN-gamma without risking immunopathology by dysregulated production of this highly potent proinflammatory cytokine.
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CD8(+) T cells armed with retrovirally transduced IFN-gamma.
Article
2018-06-13T00:06:40Z
Interferon-gamma (IFN-gamma) is considered a key cytokine involved in the preventive and defensive responses of T cells against infectious pathogens and tumors. Therefore, the transgenic expression of IFN-gamma in specific T cells appears to be an obvious therapeutic possibility. To directly examine whether IFN-gamma production can be increased in T cells, we introduced an IFN-gamma encoding cDNA into IFN-gamma(-/-) and IFN-gamma(+/+) CD8(+) effector populations by retroviral transduction. Here, we show that CD8 T cells can be equipped with IFN-gamma that increases their capacity to secrete the cytokine. Despite constitutive retroviral IFN-gamma mRNA transcription, translation and secretion of IFN-gamma protein was tightly regulated and only observed in activated T cells. Neither proliferation nor cytolytic activity of CTL was affected by IFN-gamma transduction. Importantly, CD8(+) T cells retrovirally transduced with IFN-gamma exhibit augmented tumor suppressive capacity upon adoptive transfer into IFN-gamma(-/-) mice. Thus, T cells can be readily armed with IFN-gamma without risking immunopathology by dysregulated production of this highly potent proinflammatory cytokine.
ORIGINAL
Becker et al.pdf
Becker et al.pdf
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10033/12858
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2019-08-30 11:24:31.607
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/145442019-08-30T11:33:57Zcom_10033_6804com_10033_6799col_10033_6883
Pfoertner, Susanne
915758639af9e306209e55badfae8169
500
Jeron, Andreas
2a74a8f4c70f434de4f2c7e67bb547ab
500
Probst-Kepper, Michael
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500
Guzman, Carlos A
1dc6fd50b3a3354f74ef8672c521d5c7
500
Hansen, Wiebke
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500
Westendorf, Astrid M
7da4870c7b053b85833a7aa6ea9c1423
500
Toepfer, Tanja
3547289c47010d31da91dab70f1ec916
500
Schrader, Andres J
5eae844f5bb4044ecb29f8cf4f532533
500
Franzke, Anke
2e6e3fc22942592e22ddf67b63db4050
500
Buer, Jan
0bc7f6a1fc536d7a99daf43ff0b3c37f
500
Geffers, Robert
9b3bb6a9df0a5d94975176f31cbd0bf7
500
2007-11-13T12:06:04Z
2007-11-13T12:06:04Z
2006
Genome Biol. 2006, 7(7):R54
1465-6914
16836768
10.1186/gb-2006-7-7-r54
http://hdl.handle.net/10033/14544
BACKGROUND: Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined. RESULTS: To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (Human TReg Chip) based on whole genome transcription data from human and mouse TReg cells. TReg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in TReg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in TReg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human TReg cell function. CONCLUSION: The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human TReg cells. The Human TReg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate TReg cells under physiologic and diseased conditions.
1004415 bytes
application/pdf
YES
en
Signatures of human regulatory T cells: an encounter with old friends and new players.
Article
2018-06-13T01:15:37Z
BACKGROUND: Naturally occurring CD4+ CD25+ regulatory T cells (TReg) are involved in the control of autoimmune diseases, transplantation tolerance, and anti-tumor immunity. Thus far, genomic studies on TReg cells were restricted to murine systems, and requirements for their development, maintenance, and mode of action in humans are poorly defined. RESULTS: To improve characterization of human TReg cells, we compiled a unique microarray consisting of 350 TReg cell associated genes (Human TReg Chip) based on whole genome transcription data from human and mouse TReg cells. TReg cell specific gene signatures were created from 11 individual healthy donors. Statistical analysis identified 62 genes differentially expressed in TReg cells, emphasizing some cross-species differences between mice and humans. Among them, several 'old friends' (including FOXP3, CTLA4, and CCR7) that are known to be involved in TReg cell function were recovered. Strikingly, the vast majority of genes identified had not previously been associated with human TReg cells (including LGALS3, TIAF1, and TRAF1). Most of these 'new players' however, have been described in the pathogenesis of autoimmunity. Real-time RT-PCR of selected genes validated our microarray results. Pathway analysis was applied to extract signaling modules underlying human TReg cell function. CONCLUSION: The comprehensive set of genes reported here provides a defined starting point to unravel the unique characteristics of human TReg cells. The Human TReg Chip constructed and validated here is available to the scientific community and is a useful tool with which to study the molecular mechanisms that orchestrate TReg cells under physiologic and diseased conditions.
ORIGINAL
Pfoertner et al.pdf
Pfoertner et al.pdf
original publication
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true
LICENSE
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THUMBNAIL
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10033/14544
oai:hzi.openrepository.com:10033/14544
2019-08-30 11:33:57.199
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/145462019-08-30T11:34:22Zcom_10033_6804com_10033_6799col_10033_6883
Bruder, Dunja
b5a4f0fe11461388fa1e79487e3fb00e
600
http://orcid.org/0000-0003-3066-189X
Nussbaum, Alexander K
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Gakamsky, Dimitry M
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500
Schirle, Markus
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Stevanovic, Stefan
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500
Singh-Jasuja, Harpreet
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Darji, Ayub
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Chakraborty, Trinad
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Schild, Hansjörg
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Pecht, Israel
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Weiss, Siegfried
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2007-11-13T12:24:19Z
2007-11-13T12:24:19Z
2006-01-01
Int. Immunol. 2006, 18(1):89-100
0953-8178
16291651
10.1093/intimm/dxh352
http://hdl.handle.net/10033/14546
Immunodominance in CD8+ T cell responses against Listeria monocytogenes is a well-recognized but still not fully understood phenomenon. From listeriolysin, the major virulence factor of L. monocytogenes, only a single epitope, pLLO91-99, is presented by MHC class I molecules in BALB/c mice which dominates the cytotoxic T cell response against this bacterial pathogen. To obtain more insights into the molecular and cellular mechanisms underlying immunodominance of this particular epitope, we compared the various steps involved in the presentation and recognition of pLLO91-99 derived from a wild-type toxin with an equivalent epitope from a mutated toxin. This fully functional variant contains within the pLLO91-99 epitope a conservative isoleucine to alanine replacement at the C-terminal anchor residue which results in loss of antigenicity. The binding properties of the variant peptide to soluble Kd remained unaffected and cytotoxic T cells capable of recognizing the pLLO99A/Kd complex were detectable in BALB/c mice. However, such T cells required higher concentrations of antigen in order to be optimally activated in vitro. A comparison between the TAP translocation efficiency of wild-type and mutant peptide demonstrated that the mutation at the C-terminus leads to a reduced transportation rate. Furthermore, the amino acid substitution changes the in vitro proteasomal cleavage pattern, resulting in a reduced liberation of the correct peptide from a polypeptide precursor. Thus, in all assays employed the immunodominant epitope performs optimally while the variant was found to be inferior. The synergy of all these steps most likely is the decisive factor in the immunodominance of pLLO91-99.
358931 bytes
application/pdf
YES
en
Multiple synergizing factors contribute to the strength of the CD8+ T cell response against listeriolysin O.
Article
2018-06-13T05:26:57Z
Immunodominance in CD8+ T cell responses against Listeria monocytogenes is a well-recognized but still not fully understood phenomenon. From listeriolysin, the major virulence factor of L. monocytogenes, only a single epitope, pLLO91-99, is presented by MHC class I molecules in BALB/c mice which dominates the cytotoxic T cell response against this bacterial pathogen. To obtain more insights into the molecular and cellular mechanisms underlying immunodominance of this particular epitope, we compared the various steps involved in the presentation and recognition of pLLO91-99 derived from a wild-type toxin with an equivalent epitope from a mutated toxin. This fully functional variant contains within the pLLO91-99 epitope a conservative isoleucine to alanine replacement at the C-terminal anchor residue which results in loss of antigenicity. The binding properties of the variant peptide to soluble Kd remained unaffected and cytotoxic T cells capable of recognizing the pLLO99A/Kd complex were detectable in BALB/c mice. However, such T cells required higher concentrations of antigen in order to be optimally activated in vitro. A comparison between the TAP translocation efficiency of wild-type and mutant peptide demonstrated that the mutation at the C-terminus leads to a reduced transportation rate. Furthermore, the amino acid substitution changes the in vitro proteasomal cleavage pattern, resulting in a reduced liberation of the correct peptide from a polypeptide precursor. Thus, in all assays employed the immunodominant epitope performs optimally while the variant was found to be inferior. The synergy of all these steps most likely is the decisive factor in the immunodominance of pLLO91-99.
ORIGINAL
Bruder et al_final.pdf
Bruder et al_final.pdf
original document
application/pdf
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MD5
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LICENSE
license.txt
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Bruder et al_final.pdf.txt
Bruder et al_final.pdf.txt
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10033/14546
oai:hzi.openrepository.com:10033/14546
2019-08-30 11:34:22.518
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/153382019-08-30T11:31:49Zcom_10033_6804com_10033_6799col_10033_6883
Timmerbeul, Inke
5bcbc747011365824a47278658ac3a89
500
Garrett-Engele, Carrie M
d49783ea431d20eeb7f5d2894f6d4460
500
Kossatz, Uta
38351641c50ebb52240414b2d58c84be
500
Chen, Xueyan
b13613e49a0100e5d1002c5974c2df2d
500
Firpo, Eduardo
5d96e396e82a51b762afd30fba0664d8
500
Grünwald, Viktor
0ac142b64f24d1cb72707b683deb9e2b
500
Kamino, Kenji
24f3c9ddefb17c4b190ca26a3f0216a4
500
Wilkens, Ludwig
09df544132bec406ee7c67a6234d48ec
500
Lehmann, Ulrich
ff233d0954d32aa4d976ab25ac805d2d
500
Buer, Jan
0bc7f6a1fc536d7a99daf43ff0b3c37f
500
Geffers, Robert
9b3bb6a9df0a5d94975176f31cbd0bf7
500
Kubicka, Stefan
3eddc4e05c7e7eef0c3333e128d42d04
500
Manns, Michael P
f33bb6ad494a93c8a2945a42e8e6e545
500
Porter, Peggy L
5c3c5c2480e704f1571afaa24ed0f803
500
Roberts, James M
84a18deabe8081c0c80b8dadc43e0f33
500
Malek, Nisar P
c99dd6b2f5a1d06408505df5434e79be
500
Department of Gastroenterology, Hepatology, and Endocrinology, Institute for Molecular Biology, Department of Hematology and Oncology, Institute for Pathology, Hannover Medical School, D-30625 Hannover, Germany.
2007-12-17T15:22:03Z
2007-12-17T15:22:03Z
2006-09-19
Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer. 2006, 103 (38):14009-14 Proc. Natl. Acad. Sci. U.S.A.
0027-8424
16966613
10.1073/pnas.0606316103
http://hdl.handle.net/10033/15338
Proceedings of the National Academy of Sciences of the United States of America
Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality. It is thought that decreased p27 expression in tumors is caused by increased proteasomal turnover, in particular activation of the pathway governed by the SCFskp2 E3 ubiquitin protein ligase. We have directly tested the importance of the SCFskp-mediated degradation of p27 in tumorigenesis by analyzing the tumor susceptibility of mice that express a form of p27 that cannot be ubiquitinated and degraded by this pathway (p27T187A). In mouse models of both lung and colon cancer down-regulation of p27 promotes tumorigenesis. However, we found that preventing p27 degradation by the SCFskp2 pathway had no impact on tumor incidence or overall survival in either tumor model. Our study unveiled a previously unrecognized role for the control of p27 mRNA abundance in the development of non-small cell lung cancers. In the colon cancer model, the frequency of intestinal adenomas was similarly unaffected by the p27T187A mutation, but, unexpectedly, we found that it inhibited progression of intestinal adenomas to carcinomas. These studies may guide the choice of clinical settings in which pharmacologic inhibitors of the Skp2 pathway might be of therapeutic value.
en
Animals
Cell Transformation, Neoplastic
Colonic Neoplasms
Cyclin-Dependent Kinase Inhibitor p27
Disease Models, Animal
Disease Progression
Genes, ras
Humans
Lung Neoplasms
Mice
Mice, Inbred C57BL
Mice, Knockout
Protein Kinase Inhibitors
RNA, Messenger
S-Phase Kinase-Associated Proteins
Signal Transduction
Survival Rate
Ubiquitin
Testing the importance of p27 degradation by the SCFskp2 pathway in murine models of lung and colon cancer.
Article
2018-06-12T17:15:44Z
Decreased expression of the CDK inhibitor p27kip1 in human tumors directly correlates with increased resistance to chemotherapies, increased rates of metastasis, and an overall increased rate of patient mortality. It is thought that decreased p27 expression in tumors is caused by increased proteasomal turnover, in particular activation of the pathway governed by the SCFskp2 E3 ubiquitin protein ligase. We have directly tested the importance of the SCFskp-mediated degradation of p27 in tumorigenesis by analyzing the tumor susceptibility of mice that express a form of p27 that cannot be ubiquitinated and degraded by this pathway (p27T187A). In mouse models of both lung and colon cancer down-regulation of p27 promotes tumorigenesis. However, we found that preventing p27 degradation by the SCFskp2 pathway had no impact on tumor incidence or overall survival in either tumor model. Our study unveiled a previously unrecognized role for the control of p27 mRNA abundance in the development of non-small cell lung cancers. In the colon cancer model, the frequency of intestinal adenomas was similarly unaffected by the p27T187A mutation, but, unexpectedly, we found that it inhibited progression of intestinal adenomas to carcinomas. These studies may guide the choice of clinical settings in which pharmacologic inhibitors of the Skp2 pathway might be of therapeutic value.
ORIGINAL
Timmerbeul et al_final.pdf
Timmerbeul et al_final.pdf
original manuscript
application/pdf
612200
https://hzi.openrepository.com/bitstream/10033/15338/1/Timmerbeul%20et%20al_final.pdf
09593e5ab6c75baa03c85b3953bd093c
MD5
1
true
LICENSE
license.txt
license.txt
text/plain
1783
https://hzi.openrepository.com/bitstream/10033/15338/2/license.txt
e251a97c6e39c802f9cc21ae7fe32b83
MD5
2
false
TEXT
Timmerbeul et al_final.pdf.txt
Timmerbeul et al_final.pdf.txt
Extracted Text
text/plain
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https://hzi.openrepository.com/bitstream/10033/15338/5/Timmerbeul%20et%20al_final.pdf.txt
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MD5
5
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THUMBNAIL
Timmerbeul et al_final.pdf.jpg
Timmerbeul et al_final.pdf.jpg
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10033/15338
oai:hzi.openrepository.com:10033/15338
2019-08-30 11:31:49.518
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/159172019-08-30T11:35:39Zcom_10033_6804com_10033_6799col_10033_6883
Loessner, Holger
ba246de7aa64dd46685f1388e1b4136e
500
Endmann, Anne
1b533453c68f259403b9330cae9acecb
500
Rohde, Manfred
9d59d6cfa4e7b93322b57bce461b1a4f
500
Curtiss, Roy
4695a20676250344dfdd58653720d2c9
500
Weiss, Siegfried
2d17d733cc02ae4908b4c002ef13f553
500
Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. holger.loessner@helmholtz-hzi.de
2008-01-10T11:23:31Z
2008-01-10T11:23:31Z
2006-12
Differential effect of auxotrophies on the release of macromolecules by Salmonella enterica vaccine strains. 2006, 265 (1):81-8 FEMS Microbiol. Lett.
0378-1097
17034415
10.1111/j.1574-6968.2006.00470.x
http://hdl.handle.net/10033/15917
FEMS microbiology letters
Attenuated Salmonella enterica strains have been widely used as live carriers for vaccines and therapeutic molecules. Appropriate attenuation has been introduced into such bacteria for safety reasons and the improvement of strain properties. Here, we compared two strains that were rendered auxotroph for diaminopimelic acid or thymidine monophosphate precursors by deletion of the genes asd or thyA, respectively. Upon removal of the complementing compound from bacterial cultures, both strains quickly lose their property to form colonies. However, while the Deltaasd bacteria lysed almost immediately under such conditions, DeltathyA bacteria remained physically intact during the observation period. As a consequence, the Deltaasd bacteria released their intracellular content such as proteins or plasmids into the supernatant. In contrast, no intracellular component, either proteins or plasmids, could be recovered from the supernatants of DeltathyA bacteria upon depletion of thymidine. Thus, the release of macromolecules from the bacterial carrier occurs as a consequence of appropriate lethal attenuation. This might substitute for sophisticated secretion systems.
en
Amino Acid Oxidoreductases
DNA, Bacterial
Microscopy, Electron
Plasmids
Salmonella Vaccines
Salmonella enterica
Thymidine
Thymidylate Synthase
Vaccines, Attenuated
Differential effect of auxotrophies on the release of macromolecules by Salmonella enterica vaccine strains.
Article
2018-06-13T07:18:44Z
Attenuated Salmonella enterica strains have been widely used as live carriers for vaccines and therapeutic molecules. Appropriate attenuation has been introduced into such bacteria for safety reasons and the improvement of strain properties. Here, we compared two strains that were rendered auxotroph for diaminopimelic acid or thymidine monophosphate precursors by deletion of the genes asd or thyA, respectively. Upon removal of the complementing compound from bacterial cultures, both strains quickly lose their property to form colonies. However, while the Deltaasd bacteria lysed almost immediately under such conditions, DeltathyA bacteria remained physically intact during the observation period. As a consequence, the Deltaasd bacteria released their intracellular content such as proteins or plasmids into the supernatant. In contrast, no intracellular component, either proteins or plasmids, could be recovered from the supernatants of DeltathyA bacteria upon depletion of thymidine. Thus, the release of macromolecules from the bacterial carrier occurs as a consequence of appropriate lethal attenuation. This might substitute for sophisticated secretion systems.
ORIGINAL
Loessner et al_final.pdf
Loessner et al_final.pdf
original document
application/pdf
197770
https://hzi.openrepository.com/bitstream/10033/15917/1/Loessner%20et%20al_final.pdf
f28c719e1a00b81741c7653c44c13b4d
MD5
1
true
figure-1 Loessner et al..ppt
figure-1 Loessner et al..ppt
figure 1
application/vnd.ms-powerpoint
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https://hzi.openrepository.com/bitstream/10033/15917/2/figure-1%20Loessner%20et%20al..ppt
fe733e07901352ac3bb0012a64db8733
MD5
2
false
figure-2 Loessner et al..ppt
figure-2 Loessner et al..ppt
figure 2
application/vnd.ms-powerpoint
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https://hzi.openrepository.com/bitstream/10033/15917/3/figure-2%20Loessner%20et%20al..ppt
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MD5
3
false
figure-3 Loessner et al..ppt
figure-3 Loessner et al..ppt
figure 3
application/vnd.ms-powerpoint
1735680
https://hzi.openrepository.com/bitstream/10033/15917/4/figure-3%20Loessner%20et%20al..ppt
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MD5
4
false
figure-4 Loessner et al..ppt
figure-4 Loessner et al..ppt
figure 4
application/vnd.ms-powerpoint
68096
https://hzi.openrepository.com/bitstream/10033/15917/5/figure-4%20Loessner%20et%20al..ppt
19a60154ccc1f648fb5872423d5f9110
MD5
5
false
figure-5 Loessner et al..ppt
figure-5 Loessner et al..ppt
figure 5
application/vnd.ms-powerpoint
34304
https://hzi.openrepository.com/bitstream/10033/15917/6/figure-5%20Loessner%20et%20al..ppt
5d70ffd21012865357f380818834d02e
MD5
6
false
Supplementary Figure-1 Loessner et al..ppt
Supplementary Figure-1 Loessner et al..ppt
complementary figure 1
application/vnd.ms-powerpoint
182784
https://hzi.openrepository.com/bitstream/10033/15917/7/Supplementary%20Figure-1%20Loessner%20et%20al..ppt
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MD5
7
false
LICENSE
license.txt
license.txt
text/plain
1783
https://hzi.openrepository.com/bitstream/10033/15917/8/license.txt
053fc7aaa6404e85523d049dfc27bcfe
MD5
8
false
TEXT
Loessner et al_final.pdf.txt
Loessner et al_final.pdf.txt
Extracted Text
text/plain
33738
https://hzi.openrepository.com/bitstream/10033/15917/23/Loessner%20et%20al_final.pdf.txt
73f58cc1a6713f1a9bc93c893b5df923
MD5
23
false
figure-1 Loessner et al..ppt.txt
figure-1 Loessner et al..ppt.txt
Extracted text
text/plain
111
https://hzi.openrepository.com/bitstream/10033/15917/24/figure-1%20Loessner%20et%20al..ppt.txt
5d17a82983f77179a401f2eb7f764814
MD5
24
false
figure-2 Loessner et al..ppt.txt
figure-2 Loessner et al..ppt.txt
Extracted text
text/plain
60
https://hzi.openrepository.com/bitstream/10033/15917/25/figure-2%20Loessner%20et%20al..ppt.txt
636bad0b0b9c864aa677034dc41335ee
MD5
25
false
figure-3 Loessner et al..ppt.txt
figure-3 Loessner et al..ppt.txt
Extracted text
text/plain
37
https://hzi.openrepository.com/bitstream/10033/15917/26/figure-3%20Loessner%20et%20al..ppt.txt
45de8ea0cc2b2366cd0e727b48a05720
MD5
26
false
figure-4 Loessner et al..ppt.txt
figure-4 Loessner et al..ppt.txt
Extracted text
text/plain
281
https://hzi.openrepository.com/bitstream/10033/15917/27/figure-4%20Loessner%20et%20al..ppt.txt
89d8c3dc23268773bcc7cc32c173a13d
MD5
27
false
figure-5 Loessner et al..ppt.txt
figure-5 Loessner et al..ppt.txt
Extracted text
text/plain
124
https://hzi.openrepository.com/bitstream/10033/15917/28/figure-5%20Loessner%20et%20al..ppt.txt
464644a09ff4e058688fbd6967dd4e81
MD5
28
false
Supplementary Figure-1 Loessner et al..ppt.txt
Supplementary Figure-1 Loessner et al..ppt.txt
Extracted text
text/plain
562
https://hzi.openrepository.com/bitstream/10033/15917/29/Supplementary%20Figure-1%20Loessner%20et%20al..ppt.txt
5790ad4f806b7a17e3b520657369ad6b
MD5
29
false
THUMBNAIL
figure-1 Loessner et al..ppt.jpg
figure-1 Loessner et al..ppt.jpg
Generated Thumbnail
image/jpeg
5453
https://hzi.openrepository.com/bitstream/10033/15917/31/figure-1%20Loessner%20et%20al..ppt.jpg
fcfd34ff39b52148e33f58fbc7108ae9
MD5
31
false
figure-2 Loessner et al..ppt.jpg
figure-2 Loessner et al..ppt.jpg
Generated Thumbnail
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2019-08-30 11:35:39.443
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/162762019-08-30T11:36:05Zcom_10033_6804com_10033_6799col_10033_6883
Coldewey, Sina M
962e1b1129eced89316cc1af21ec820d
500
Hartmann, Maike
33baed6ff68a4522ecaa6d7ee3e8d1f1
500
Schmidt, Dorothea S
68231f8de425317f009ef6771f006442
500
Engelking, Uta
f22988b023b070fb4db29481bce28793
500
Ukena, Sya N
958b5b134503d0b1908f9fe8c2b82f47
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Gunzer, Florian
052a429c33e35f043f0de374c4f9d5b9
500
Institute for Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany. sina.coldewey@web.de <sina.coldewey@web.de>
2008-01-17T14:24:19Z
2008-01-17T14:24:19Z
2007
Impact of the rpoS genotype for acid resistance patterns of pathogenic and probiotic Escherichia coli. 2007, 7:21 BMC Microbiol.
1471-2180
17386106
10.1186/1471-2180-7-21
http://hdl.handle.net/10033/16276
BMC microbiology
BACKGROUND: Enterohemorrhagic E. coli (EHEC), a subgroup of Shiga toxin (Stx) producing E. coli (STEC), may cause severe enteritis and hemolytic uremic syndrome (HUS) and is transmitted orally via contaminated foods or from person to person. The infectious dose is known to be very low, which requires most of the bacteria to survive the gastric acid barrier. Acid resistance therefore is an important mechanism of EHEC virulence. It should also be a relevant characteristic of E. coli strains used for therapeutic purposes such as the probiotic E. coli Nissle 1917 (EcN). In E. coli and related enteric bacteria it has been extensively demonstrated, that the alternative sigma factor sigmaS, encoded by the rpoS gene, acts as a master regulator mediating resistance to various environmental stress factors. METHODS: Using rpoS deletion mutants of a highly virulent EHEC O26:H11 patient isolate and the sequenced prototype EHEC EDL933 (ATCC 700927) of serotype O157:H7 we investigated the impact of a functional rpoS gene for orchestrating a satisfactory response to acid stress in these strains. We then functionally characterized rpoS of probiotic EcN and five rpoS genes selected from STEC isolates pre-investigated for acid resistance. RESULTS: First, we found out that ATCC isolate 700927 of EHEC EDL933 has a point mutation in rpoS, not present in the published sequence, leading to a premature stop codon. Moreover, to our surprise, one STEC strain as well as EcN was acid sensitive in our test environment, although their cloned rpoS genes could effectively complement acid sensitivity of an rpoS deletion mutant. CONCLUSION: The attenuation of sequenced EHEC EDL933 might be of importance for anyone planning to do either in vitro or in vivo studies with this prototype strain. Furthermore our data supports recently published observations, that individual E. coli isolates are able to significantly modulate their acid resistance phenotype independent of their rpoS genotype.
en
Acids
Base Sequence
Drug Resistance, Bacterial
Escherichia coli
Escherichia coli O157
Escherichia coli Proteins
Gene Expression Regulation, Bacterial
Genetic Complementation Test
Genotype
Hydrogen-Ion Concentration
Molecular Sequence Data
Point Mutation
Probiotics
Sequence Alignment
Sigma Factor
Impact of the rpoS genotype for acid resistance patterns of pathogenic and probiotic Escherichia coli.
Article
2018-06-13T02:26:19Z
BACKGROUND: Enterohemorrhagic E. coli (EHEC), a subgroup of Shiga toxin (Stx) producing E. coli (STEC), may cause severe enteritis and hemolytic uremic syndrome (HUS) and is transmitted orally via contaminated foods or from person to person. The infectious dose is known to be very low, which requires most of the bacteria to survive the gastric acid barrier. Acid resistance therefore is an important mechanism of EHEC virulence. It should also be a relevant characteristic of E. coli strains used for therapeutic purposes such as the probiotic E. coli Nissle 1917 (EcN). In E. coli and related enteric bacteria it has been extensively demonstrated, that the alternative sigma factor sigmaS, encoded by the rpoS gene, acts as a master regulator mediating resistance to various environmental stress factors. METHODS: Using rpoS deletion mutants of a highly virulent EHEC O26:H11 patient isolate and the sequenced prototype EHEC EDL933 (ATCC 700927) of serotype O157:H7 we investigated the impact of a functional rpoS gene for orchestrating a satisfactory response to acid stress in these strains. We then functionally characterized rpoS of probiotic EcN and five rpoS genes selected from STEC isolates pre-investigated for acid resistance. RESULTS: First, we found out that ATCC isolate 700927 of EHEC EDL933 has a point mutation in rpoS, not present in the published sequence, leading to a premature stop codon. Moreover, to our surprise, one STEC strain as well as EcN was acid sensitive in our test environment, although their cloned rpoS genes could effectively complement acid sensitivity of an rpoS deletion mutant. CONCLUSION: The attenuation of sequenced EHEC EDL933 might be of importance for anyone planning to do either in vitro or in vivo studies with this prototype strain. Furthermore our data supports recently published observations, that individual E. coli isolates are able to significantly modulate their acid resistance phenotype independent of their rpoS genotype.
ORIGINAL
Coldewey et al.pdf
Coldewey et al.pdf
original Open Access Publication
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Coldewey et al.pdf.txt
Coldewey et al.pdf.txt
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MD5
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THUMBNAIL
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2019-08-30 11:36:05.428
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/191782019-08-30T11:36:32Zcom_10033_6804com_10033_6799col_10033_6883
Stecher, Bärbel
379c8adc65a3187803c351215d5aaa11
500
Robbiani, Riccardo
e4339160a6d8a3512d4ae5867ceabe0d
500
Walker, Alan W
774d133b6c550829338881841ef4f7fa
500
Westendorf, Astrid M
7da4870c7b053b85833a7aa6ea9c1423
500
Barthel, Manja
5c2df6c16eac5d98c1d12d97234c23d5
500
Kremer, Marcus
95a2bb1d7a2cd1664da3741fd8147e7a
500
Chaffron, Samuel
41d11ca381b7fc4a4ea8fadf3636af53
500
Macpherson, Andrew J
64266fe8041d5ecf99df52d2d3268dcb
500
Buer, Jan
0bc7f6a1fc536d7a99daf43ff0b3c37f
500
Parkhill, Julian
2725d4556af2a8c6288bb04de62173dd
500
Dougan, Gordon
0dacb9198028a80fdb992d8d31a44b34
500
von Mering, Christian
f466c230b8e38e067b5ee5330df122fd
500
Hardt, Wolf-Dietrich
448c3c121c39f59cdf718ec074942bfc
500
Institute of Microbiology, Swiss Institute of Technology Zurich, Zurich, Switzerland.
2008-02-26T14:00:54Z
2008-02-26T14:00:54Z
2007-10
Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota. 2007, 5 (10):2177-89 PLoS Biol.
1545-7885
17760501
10.1371/journal.pbio.0050244
http://hdl.handle.net/10033/19178
PLoS biology
Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.
en
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17760501
Animals
Bacteria
Colitis
Female
Genotype
In Situ Hybridization, Fluorescence
Intestines
Male
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred Strains
Microscopy, Fluorescence
Models, Animal
Molecular Sequence Data
Mutation
Phylogeny
RNA, Ribosomal, 16S
Salmonella Infections
Salmonella typhimurium
Sequence Analysis, DNA
Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota.
Article
2018-06-13T02:24:37Z
Most mucosal surfaces of the mammalian body are colonized by microbial communities ("microbiota"). A high density of commensal microbiota inhabits the intestine and shields from infection ("colonization resistance"). The virulence strategies allowing enteropathogenic bacteria to successfully compete with the microbiota and overcome colonization resistance are poorly understood. Here, we investigated manipulation of the intestinal microbiota by the enteropathogenic bacterium Salmonella enterica subspecies 1 serovar Typhimurium (S. Tm) in a mouse colitis model: we found that inflammatory host responses induced by S. Tm changed microbiota composition and suppressed its growth. In contrast to wild-type S. Tm, an avirulent invGsseD mutant failing to trigger colitis was outcompeted by the microbiota. This competitive defect was reverted if inflammation was provided concomitantly by mixed infection with wild-type S. Tm or in mice (IL10(-/-), VILLIN-HA(CL4-CD8)) with inflammatory bowel disease. Thus, inflammation is necessary and sufficient for overcoming colonization resistance. This reveals a new concept in infectious disease: in contrast to current thinking, inflammation is not always detrimental for the pathogen. Triggering the host's immune defence can shift the balance between the protective microbiota and the pathogen in favour of the pathogen.
CC-LICENSE
license_url
license_url
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https://hzi.openrepository.com/bitstream/10033/19178/1/license_url
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ORIGINAL
stecher et al_final.pdf
stecher et al_final.pdf
Open Access publication
application/pdf
1411778
https://hzi.openrepository.com/bitstream/10033/19178/5/stecher%20et%20al_final.pdf
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MD5
5
true
TEXT
stecher et al_final.pdf.txt
stecher et al_final.pdf.txt
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https://hzi.openrepository.com/bitstream/10033/19178/8/stecher%20et%20al_final.pdf.txt
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8
false
THUMBNAIL
stecher et al_final.pdf.jpg
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10033/19178
oai:hzi.openrepository.com:10033/19178
2019-08-30 11:36:32.792
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/251532019-08-30T11:26:42Zcom_10033_6804com_10033_6799col_10033_6883
Trebst, Corinna
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Heine, Sandra
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Lienenklaus, Stefan
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Lindner, Maren
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Baumgärtner, Wolfgang
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Weiss, Siegfried
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Stangel, Martin
c34c7db9fb99df1894fa38347613609e
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Department of Neurology, Medical School Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
2008-05-08T14:10:16Z
2008-05-08T14:10:16Z
2007-12
Lack of interferon-beta leads to accelerated remyelination in a toxic model of central nervous system demyelination. 2007, 114 (6):587-96 Acta Neuropathol.
0001-6322
17940777
10.1007/s00401-007-0300-z
http://hdl.handle.net/10033/25153
Acta neuropathologica
Interferon-beta (IFN-beta) is a pleiotropic cytokine that is known to modulate the immune response in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Spontaneous remyelination and repair mechanisms in MS are mostly insufficient and contribute to clinical disability. Here, we investigated whether IFN-beta has a potential in modifying the extent of de- and remyelination in a toxic model of CNS demyelination induced by the copper chelator cuprizone. IFN-beta deficient (k/o) mice showed an accelerated spontaneous remyelination. However, the amount of remyelination after 6 weeks did not differ between the two groups. Demyelination in IFN-beta k/o mice was paralleled by a diminished astrocytic and microglia response as compared with wildtype controls, whereas the accelerated remyelination was paralleled by an increased number of oligodendrocyte precursor cells (OPC) within the demyelinated lesion at the beginning of the remyelination phase. We hypothesize that the absence of IFN-beta leads to more efficient recruitment and proliferation of OPC already during demyelination, thus allowing early remyelination. These results demonstrate that IFN-beta is able to alter remyelination in the absence of an immune-mediated demyelination.
en
Animals
Astrocytes
Axons
Chelating Agents
Cuprizone
Disease Models, Animal
Gliosis
Interferon-beta
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Microglia
Microscopy, Electron, Transmission
Multiple Sclerosis
Myelin Sheath
Recovery of Function
Lack of interferon-beta leads to accelerated remyelination in a toxic model of central nervous system demyelination.
Article
2008-12-05T00:00:00Z
Interferon-beta (IFN-beta) is a pleiotropic cytokine that is known to modulate the immune response in multiple sclerosis (MS), an inflammatory demyelinating disease of the central nervous system (CNS). Spontaneous remyelination and repair mechanisms in MS are mostly insufficient and contribute to clinical disability. Here, we investigated whether IFN-beta has a potential in modifying the extent of de- and remyelination in a toxic model of CNS demyelination induced by the copper chelator cuprizone. IFN-beta deficient (k/o) mice showed an accelerated spontaneous remyelination. However, the amount of remyelination after 6 weeks did not differ between the two groups. Demyelination in IFN-beta k/o mice was paralleled by a diminished astrocytic and microglia response as compared with wildtype controls, whereas the accelerated remyelination was paralleled by an increased number of oligodendrocyte precursor cells (OPC) within the demyelinated lesion at the beginning of the remyelination phase. We hypothesize that the absence of IFN-beta leads to more efficient recruitment and proliferation of OPC already during demyelination, thus allowing early remyelination. These results demonstrate that IFN-beta is able to alter remyelination in the absence of an immune-mediated demyelination.
ORIGINAL
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oai:hzi.openrepository.com:10033/25153
2019-08-30 11:26:42.941
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/281522019-08-30T11:26:42Zcom_10033_6804com_10033_6799col_10033_6883
Bleich, Andre
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500
Sundberg, John P
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500
Smoczek, Anna
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500
von Wasielewski, Reinhard
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de Buhr, Maike F
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Janus, Lydia M
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Julga, Gwen
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Ukena, Sya N
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Hedrich, Hans-J
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Gunzer, Florian
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Institute for Laboratory Animal Science and Central Animal Facility, Hannover Medical School, Hannover, Germany. bleich.andre@mh-hannover.de
2008-05-26T13:15:34Z
2008-05-26T13:15:34Z
2008-02
Sensitivity to Escherichia coli Nissle 1917 in mice is dependent on environment and genetic background. 2008, 89 (1):45-54notInt J Exp Pathol
1365-2613
18005134
10.1111/j.1365-2613.2007.00560.x
http://hdl.handle.net/10033/28152
International journal of experimental pathology
Escherichia coli Nissle 1917 (EcN) is a well-characterized probiotic bacterium. Although genomic comparisons of EcN with the uropathogenic E. coli strain CFT073 revealed high degrees of similarity, EcN is generally considered a non-pathogenic organism. However, as recent evidence suggests that EcN is capable of inducing inflammatory responses in host intestinal epithelial cells, we aimed to investigate potential pathogenic properties of EcN in an in vivo model using various germ-free (GF) mouse strains. With the exception of C3H/HeJZtm mice, which carry a defective toll-like receptor (TLR)4-allele, no lesions were obvious in mice of different strains orally inoculated with EcN for 1 week, although organ cultures (blood, lung, mesenteric lymph node, pancreas, spleen, liver and kidney) tested positive to various degrees. C3H/HeJZtm mice inoculated with EcN became clinically ill and the majority died or had to be euthanized. Organs of all gnotobiotic C3H/HeJZtm mice were positive for EcN by culture; major histological findings were moderate to severe pyogranulomatous serositis, typhlitis and pancreatitis. Histological findings were corroborated by highly elevated tumour necrosis factor (TNF) serum levels. Lesions were not detected in specified pathogen free maintained C3H/HeJZtm mice, GF C3H/HeJ mice lacking the interleukin-10 gene, or GF C3H/HeJZtm mice that were inoculated with E. coli K12 strain MG1655 as a control. In addition, mild histological lesions were detected in Ztm:NMRI mice 3 months after oral inoculation with EcN. This study shows that EcN is capable of displaying a virulent phenotype in GF C3H/HeJZtm mice. Whether this phenotype is linked to the bacterium's probiotic nature should be the focus of further studies.
en
Animals
Disease Models, Animal
Escherichia coli
Female
Germ-Free Life
Intestines
Male
Mice
Probiotics
Sensitivity and Specificity
Sensitivity to Escherichia coli Nissle 1917 in mice is dependent on environment and genetic background.
Article
2009-02-05T00:00:00Z
Escherichia coli Nissle 1917 (EcN) is a well-characterized probiotic bacterium. Although genomic comparisons of EcN with the uropathogenic E. coli strain CFT073 revealed high degrees of similarity, EcN is generally considered a non-pathogenic organism. However, as recent evidence suggests that EcN is capable of inducing inflammatory responses in host intestinal epithelial cells, we aimed to investigate potential pathogenic properties of EcN in an in vivo model using various germ-free (GF) mouse strains. With the exception of C3H/HeJZtm mice, which carry a defective toll-like receptor (TLR)4-allele, no lesions were obvious in mice of different strains orally inoculated with EcN for 1 week, although organ cultures (blood, lung, mesenteric lymph node, pancreas, spleen, liver and kidney) tested positive to various degrees. C3H/HeJZtm mice inoculated with EcN became clinically ill and the majority died or had to be euthanized. Organs of all gnotobiotic C3H/HeJZtm mice were positive for EcN by culture; major histological findings were moderate to severe pyogranulomatous serositis, typhlitis and pancreatitis. Histological findings were corroborated by highly elevated tumour necrosis factor (TNF) serum levels. Lesions were not detected in specified pathogen free maintained C3H/HeJZtm mice, GF C3H/HeJ mice lacking the interleukin-10 gene, or GF C3H/HeJZtm mice that were inoculated with E. coli K12 strain MG1655 as a control. In addition, mild histological lesions were detected in Ztm:NMRI mice 3 months after oral inoculation with EcN. This study shows that EcN is capable of displaying a virulent phenotype in GF C3H/HeJZtm mice. Whether this phenotype is linked to the bacterium's probiotic nature should be the focus of further studies.
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ORIGINAL
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oai:hzi.openrepository.com:10033/28152
2019-08-30 11:26:42.949
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/360522019-08-30T11:31:49Zcom_10033_6804com_10033_6799col_10033_6883
Depke, Maren
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Fusch, Gerhard
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Domanska, Grazyna
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Geffers, Robert
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http://orcid.org/0000-0003-4409-016X
Völker, Uwe
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Schuett, Christine
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Kiank, Cornelia
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Ernst-Moritz-Arndt-University, Interfaculty Institute of Genetics and Functional Genomics, 17487 Greifswald, Germany.
2008-08-21T09:28:28Z
2008-08-21T09:28:28Z
2008-06
Hypermetabolic syndrome as a consequence of repeated psychological stress in mice. 2008, 149 (6):2714-23 Endocrinology
0013-7227
18325986
10.1210/en.2008-0038
http://hdl.handle.net/10033/36052
Endocrinology
Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. After 4.5-d repeated combined acoustic and restraint stress as a murine model of chronic psychological stress, severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with the severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turnover, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure, changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice. Thus, in our murine model, repeated stress caused severe metabolic dysregulations, leading to a drastic reduction of the individual's energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.
en
Acoustic Stimulation
Acute Disease
Animals
Disease Models, Animal
Drinking Behavior
Energy Intake
Energy Metabolism
Female
Kinetics
Metabolic Syndrome X
Mice
Mice, Inbred BALB C
Oligonucleotide Array Sequence Analysis
Polymerase Chain Reaction
Stress, Psychological
Water
Hypermetabolic syndrome as a consequence of repeated psychological stress in mice.
Article
2018-06-13T01:15:47Z
Stress is a powerful modulator of neuroendocrine, behavioral, and immunological functions. After 4.5-d repeated combined acoustic and restraint stress as a murine model of chronic psychological stress, severe metabolic dysregulations became detectable in female BALB/c mice. Stress-induced alterations of metabolic processes that were found in a hepatic mRNA expression profiling were verified by in vivo analyses. Repeatedly stressed mice developed a hypermetabolic syndrome with the severe loss of lean body mass, hyperglycemia, dyslipidemia, increased amino acid turnover, and acidosis. This was associated with hypercortisolism, hyperleptinemia, insulin resistance, and hypothyroidism. In contrast, after a single acute stress exposure, changes in expression of metabolic genes were much less pronounced and predominantly confined to gluconeogenesis, probably indicating that metabolic disturbances might be initiated already early but will only manifest in repeatedly stressed mice. Thus, in our murine model, repeated stress caused severe metabolic dysregulations, leading to a drastic reduction of the individual's energy reserves. Under such circumstances stress may further reduce the ability to cope with new stressors such as infection or cancer.
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2019-08-30 11:31:49.515
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/872372019-08-30T11:35:14Zcom_10033_6804com_10033_6799col_10033_6883
Huys, Liesbeth
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500
Van Hauwermeiren, Filip
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Dejager, Lien
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Dejonckheere, Eline
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Lienenklaus, Stefan
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Weiss, Siegfried
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Leclercq, Georges
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Libert, Claude
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Department for Molecular Biomedical Research, VIB, Ghent B9052, Belgium.
2009-12-02T15:31:30Z
2009-12-02T15:31:30Z
2009-08-31
Type I interferon drives tumor necrosis factor-induced lethal shock. 2009, 206 (9):1873-82 J. Exp. Med.
1540-9538
19687227
10.1084/jem.20090213
http://hdl.handle.net/10033/87237
The Journal of experimental medicine
Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1(-/-) mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1(-/-) mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element-dependent genes, many of which encode chemokines. In livers of IFNAR-1(-/-) mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.
en
Animals
Gene Expression Profiling
Hypothermia
Immunohistochemistry
In Situ Nick-End Labeling
Interferon Type I
Interleukin-6
Liver
Mice
Mice, Knockout
Receptor, Interferon alpha-beta
Signal Transduction
Systemic Inflammatory Response Syndrome
Tumor Necrosis Factor-alpha
Type I interferon drives tumor necrosis factor-induced lethal shock.
Article
2018-06-12T22:08:14Z
Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1(-/-) mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1(-/-) mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element-dependent genes, many of which encode chemokines. In livers of IFNAR-1(-/-) mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.
ORIGINAL
Huys et al_final.pdf
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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Singh, Anurag
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Engelhardt, Regina
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Seidler, Ursula
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Hansen, Wiebke
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Bleich, André
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Bruder, Dunja
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http://orcid.org/0000-0003-3066-189X
Franzke, Anke
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Rogler, Gerhard
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Suerbaum, Sebastian
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Buer, Jan
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Gunzer, Florian
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Westendorf, Astrid M
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Department of Mucosal Immunity, Helmholtz Centre for Infection Research, Braunschweig, Germany.
2010-03-12T09:20:52Z
2010-03-12T09:20:52Z
2007
Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity. 2007, 2 (12):e1308 PLoS ONE
1932-6203
18074031
10.1371/journal.pone.0001308
http://hdl.handle.net/10033/94153
PloS one
BACKGROUND: Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs). METHODOLOGY AND PRINCIPAL FINDINGS: To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS) induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1. CONCLUSION AND SIGNIFICANCE: This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.
en
Animals
Base Sequence
Blotting, Western
Colitis
DNA Primers
Escherichia coli
Female
Fluorescent Antibody Technique
Germ-Free Life
Intestinal Mucosa
Mice
Mice, Inbred BALB C
Probiotics
Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.
Article
2018-06-13T09:10:25Z
BACKGROUND: Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs). METHODOLOGY AND PRINCIPAL FINDINGS: To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E. coli strain MG1655. IECs were isolated and analyzed for gene and protein expression of the tight junction molecules ZO-1 and ZO-2. Then, in order to analyze beneficial effects of EcN under inflammatory conditions, the probiotic was orally administered to BALB/c mice with acute dextran sodium sulfate (DSS) induced colitis. Colonization of gnotobiotic mice with EcN resulted in an up-regulation of ZO-1 in IECs at both mRNA and protein levels. EcN administration to DSS-treated mice reduced the loss of body weight and colon shortening. In addition, infiltration of the colon with leukocytes was ameliorated in EcN inoculated mice. Acute DSS colitis did not result in an anion secretory defect, but abrogated the sodium absorptive function of the mucosa. Additionally, intestinal barrier function was severely affected as evidenced by a strong increase in the mucosal uptake of Evans blue in vivo. Concomitant administration of EcN to DSS treated animals resulted in a significant protection against intestinal barrier dysfunction and IECs isolated from these mice exhibited a more pronounced expression of ZO-1. CONCLUSION AND SIGNIFICANCE: This study convincingly demonstrates that probiotic EcN is able to mediate up-regulation of ZO-1 expression in murine IECs and confer protection from the DSS colitis-associated increase in mucosal permeability to luminal substances.
ORIGINAL
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2019-08-30 11:35:13.935
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/959752019-08-30T11:29:17Zcom_10033_6804com_10033_6799col_10033_6883
Ukena, Sya N
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Westendorf, Astrid M
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Hansen, Wiebke
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Rohde, Manfred
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Geffers, Robert
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Coldewey, Sina
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Suerbaum, Sebastian
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Buer, Jan
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Gunzer, Florian
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German Research Centre for Biotechnology, Mucosal Immunity Group, Mascheroder Weg 1, 38124 Braunschweig, Germany. suk@gbf.de
2010-04-08T09:10:02Z
2010-04-08T09:10:02Z
2005
The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1. 2005, 6:43 BMC Med. Genet.
1471-2350
16351713
10.1186/1471-2350-6-43
http://hdl.handle.net/10033/95975
BMC medical genetics
BACKGROUND: The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. METHODS: Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA) to detect secretion of corresponding proteins. RESULTS: Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1), macrophage inflammatory protein-2 alpha (MIP-2alpha) and macrophage inflammatory protein-2 beta (MIP-2beta) was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2alpha mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. CONCLUSION: Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.
en
Biological Therapy
Caco-2 Cells
Chemokine CCL2
Chemokine CXCL2
Escherichia coli
Gene Expression Profiling
Humans
Immunotherapy
Inflammation
Intestinal Diseases
Intestines
Monokines
Probiotics
RNA, Messenger
Up-Regulation
The host response to the probiotic Escherichia coli strain Nissle 1917: specific up-regulation of the proinflammatory chemokine MCP-1.
Article
2018-06-13T02:35:12Z
BACKGROUND: The use of live microorganisms to influence positively the course of intestinal disorders such as infectious diarrhea or chronic inflammatory conditions has recently gained increasing interest as a therapeutic alternative. In vitro and in vivo investigations have demonstrated that probiotic-host eukaryotic cell interactions evoke a large number of responses potentially responsible for the effects of probiotics. The aim of this study was to improve our understanding of the E. coli Nissle 1917-host interaction by analyzing the gene expression pattern initiated by this probiotic in human intestinal epithelial cells. METHODS: Gene expression profiles of Caco-2 cells treated with E. coli Nissle 1917 were analyzed with microarrays. A second human intestinal cell line and also pieces of small intestine from BALB/c mice were used to confirm regulatory data of selected genes by real-time RT-PCR and cytometric bead array (CBA) to detect secretion of corresponding proteins. RESULTS: Whole genome expression analysis revealed 126 genes specifically regulated after treatment of confluent Caco-2 cells with E. coli Nissle 1917. Among others, expression of genes encoding the proinflammatory molecules monocyte chemoattractant protein-1 ligand 2 (MCP-1), macrophage inflammatory protein-2 alpha (MIP-2alpha) and macrophage inflammatory protein-2 beta (MIP-2beta) was increased up to 10 fold. Caco-2 cells cocultured with E. coli Nissle 1917 also secreted high amounts of MCP-1 protein. Elevated levels of MCP-1 and MIP-2alpha mRNA could be confirmed with Lovo cells. MCP-1 gene expression was also up-regulated in mouse intestinal tissue. CONCLUSION: Thus, probiotic E. coli Nissle 1917 specifically upregulates expression of proinflammatory genes and proteins in human and mouse intestinal epithelial cells.
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Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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oai:repository.helmholtz-hzi.de:10033/965972019-08-30T11:34:48Zcom_10033_6804com_10033_6799col_10033_6883
Loessner, Holger
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Leschner, Sara
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Endmann, Anne
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Westphal, Kathrin
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Wolf, Kathrin
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Kochruebe, Katja
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Miloud, Tewfik
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Altenbuchner, Josef
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Weiss, Siegfried
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Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Inhoffenstrasse 7, 38124 Braunschweig, Germany. loeho@pei.de
2010-04-15T12:06:20Z
2010-04-15T12:06:20Z
2009-12
Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice. 2009, 11 (14-15):1097-105 Microbes Infect.
1769-714X
19665575
10.1016/j.micinf.2009.08.002
http://hdl.handle.net/10033/96597
Microbes and infection / Institut Pasteur
The probiotic bacterium Escherichia coli Nissle 1917 (EcN) constitutes a prospective vector for delivering heterologous therapeutic molecules to treat several human disorders. To add versatility to this carrier system, bacteria should be equipped with expression modules that can be regulated deliberately in a temporal and quantitative manner. This approach is called in vivo remote control (IVRC) of bacterial vectors. Here, we have evaluated promoters P(araBAD), P(rhaBAD) and P(tet), which can be induced with L-arabinose, L-rhamnose or anhydrotetracycline, respectively. EcN harboring promoter constructs with luciferase as reporter gene were administered either orally to healthy mice or intravenously to tumor bearing animals. Subsequent to bacterial colonization of tissues, inducer substances were administered via the oral or systemic route. By use of in vivo bioluminescence imaging, the time course of reporter gene expression was analyzed. Each promoter displayed a specific in vivo induction profile depending on the niche of bacterial residence and the route of inducer administration. Importantly, we also observed colonization of gall bladders of mice when EcN was administered systemically at high doses. Bacteria in this anatomical compartment remained accessible to remote control of bacterial gene expression.
en
Animals
Arabinose
Cell Line, Tumor
Escherichia coli
Female
Gallbladder
Gene Expression Regulation, Bacterial
Intestines
Luciferases
Mice
Mice, Inbred BALB C
Neoplasms, Experimental
Probiotics
Promoter Regions, Genetic
Rhamnose
Skin Neoplasms
Tetracyclines
Tissue Distribution
Drug-inducible remote control of gene expression by probiotic Escherichia coli Nissle 1917 in intestine, tumor and gall bladder of mice.
Article
2018-06-13T07:21:40Z
The probiotic bacterium Escherichia coli Nissle 1917 (EcN) constitutes a prospective vector for delivering heterologous therapeutic molecules to treat several human disorders. To add versatility to this carrier system, bacteria should be equipped with expression modules that can be regulated deliberately in a temporal and quantitative manner. This approach is called in vivo remote control (IVRC) of bacterial vectors. Here, we have evaluated promoters P(araBAD), P(rhaBAD) and P(tet), which can be induced with L-arabinose, L-rhamnose or anhydrotetracycline, respectively. EcN harboring promoter constructs with luciferase as reporter gene were administered either orally to healthy mice or intravenously to tumor bearing animals. Subsequent to bacterial colonization of tissues, inducer substances were administered via the oral or systemic route. By use of in vivo bioluminescence imaging, the time course of reporter gene expression was analyzed. Each promoter displayed a specific in vivo induction profile depending on the niche of bacterial residence and the route of inducer administration. Importantly, we also observed colonization of gall bladders of mice when EcN was administered systemically at high doses. Bacteria in this anatomical compartment remained accessible to remote control of bacterial gene expression.
ORIGINAL
Loessner et al_final.pdf
Loessner et al_final.pdf
original manuscript
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Figure 1
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Figure 2
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Figure 3
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Figure 4
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Figure 5
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Figure 6
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supplementary Figure 1
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supplementary Figure 3
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CC-LICENSE
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LICENSE
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license.txt
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THUMBNAIL
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Generated Thumbnail
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Generated Thumbnail
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Generated Thumbnail
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TEXT
Loessner et al_final.pdf.txt
Loessner et al_final.pdf.txt
Extracted Text
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Loessner Figure 1.ppt.txt
Loessner Figure 1.ppt.txt
Extracted text
text/plain
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MD5
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Loessner Figure 2.ppt.txt
Loessner Figure 2.ppt.txt
Extracted text
text/plain
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https://hzi.openrepository.com/bitstream/10033/96597/37/Loessner%20Figure%202.ppt.txt
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MD5
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Loessner Figure 3.ppt.txt
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Extracted text
text/plain
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MD5
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Loessner Figure 4.ppt.txt
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Extracted text
text/plain
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MD5
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Loessner Figure 5.ppt.txt
Loessner Figure 5.ppt.txt
Extracted text
text/plain
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MD5
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Loessner Figure 6.ppt.txt
Loessner Figure 6.ppt.txt
Extracted text
text/plain
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MD5
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Loessner Suppl Figure 1.ppt.txt
Loessner Suppl Figure 1.ppt.txt
Extracted text
text/plain
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MD5
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Loessner Suppl Figure 2.ppt.txt
Loessner Suppl Figure 2.ppt.txt
Extracted text
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MD5
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Loessner Suppl Figure 3.ppt.txt
Loessner Suppl Figure 3.ppt.txt
Extracted text
text/plain
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MD5
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10033/96597
oai:hzi.openrepository.com:10033/96597
2019-08-30 11:34:48.461
Helmholtz Zentrum für Infektionsforschung Repository
hzi@openrepository.com
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