2024-03-28T09:35:21Zhttp://repository.helmholtz-hzi.de/oai/requestoai:repository.helmholtz-hzi.de:10033/3110792019-08-30T11:36:32Zcom_10033_338554com_10033_128109col_10033_621050col_10033_620747
Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ.
Trsan, Tihana
Busche, Andreas
Abram, Maja
Wensveen, Felix M
Lemmermann, Niels A
Arapovic, Maja
Babic, Marina
Tomic, Adriana
Golemac, Mijo
Brinkmann, Melanie M
Jäger, Wiebke
Oxenius, Annette
Polic, Bojan
Krmpotic, Astrid
Messerle, Martin
Jonjic, Stipan
Research group viral immune modulation, Helmholtz Centre for infection research, Braunschweig, Germany
Animals
CD8-Positive T-Lymphocytes
Cytomegalovirus
Flow Cytometry
Genetic Vectors
Immune Evasion
Listeria monocytogenes
Membrane Proteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
NK Cell Lectin-Like Receptor Subfamily K
Statistics, Nonparametric
Vaccines, Synthetic
Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.
2014-01-08T15:40:39Z
2014-01-08T15:40:39Z
2013-10-08
Article
Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ. 2013, 110 (41):16550-5 Proc. Natl. Acad. Sci. U.S.A.
1091-6490
24052528
10.1073/pnas.1310215110
http://hdl.handle.net/10033/311079
Proceedings of the National Academy of Sciences of the United States of America
en
Archived with thanks to Proceedings of the National Academy of Sciences of the United States of America
oai:repository.helmholtz-hzi.de:10033/3379932019-08-30T11:36:33Zcom_10033_338554com_10033_128109col_10033_621050col_10033_620747
Age-dependent enterocyte invasion and microcolony formation by Salmonella.
Zhang, Kaiyi
Dupont, Aline
Torow, Natalia
Gohde, Fredrik
Leschner, Sara
Lienenklaus, Stefan
Weiss, Siegfried
Brinkmann, Melanie M
Kühnel, Mark
Hensel, Michael
Fulde, Marcus
Hornef, Mathias W
The coordinated action of a variety of virulence factors allows Salmonella enterica to invade epithelial cells and penetrate the mucosal barrier. The influence of the age-dependent maturation of the mucosal barrier for microbial pathogenesis has not been investigated. Here, we analyzed Salmonella infection of neonate mice after oral administration. In contrast to the situation in adult animals, we observed spontaneous colonization, massive invasion of enteroabsorptive cells, intraepithelial proliferation and the formation of large intraepithelial microcolonies. Mucosal translocation was dependent on enterocyte invasion in neonates in the absence of microfold (M) cells. It further resulted in potent innate immune stimulation in the absence of pronounced neutrophil-dominated pathology. Our results identify factors of age-dependent host susceptibility and provide important insight in the early steps of Salmonella infection in vivo. We also present a new small animal model amenable to genetic manipulation of the host for the analysis of the Salmonella enterocyte interaction in vivo.
2015-01-09T15:35:49Z
2015-01-09T15:35:49Z
2014-09
Article
Age-dependent enterocyte invasion and microcolony formation by Salmonella. 2014, 10 (9):e1004385 PLoS Pathog.
1553-7374
25210785
10.1371/journal.ppat.1004385
http://hdl.handle.net/10033/337993
PLoS pathogens
en
oai:repository.helmholtz-hzi.de:10033/6212262019-08-30T11:30:58Zcom_10033_128109col_10033_620747
IRAP+ endosomes restrict TLR9 activation and signaling.
Babdor, Joel
Descamps, Delphyne
Adiko, Aimé Cézaire
Tohmé, Mira
Maschalidi, Sophia
Evnouchidou, Irini
Vasconcellos, Luiz Ricardo
De Luca, Mariacristina
Mauvais, Francois-Xavier
Garfa-Traore, Meriem
Brinkmann, Melanie M
Chignard, Michel
Manoury, Bénédicte
Saveanu, Loredana
Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Animals
Cells, Cultured
CpG Islands
Cystinyl Aminopeptidase
Cytoskeleton
Dendritic Cells
Endosomes
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation
Oligodeoxyribonucleotides
Protein Binding
Pseudomonas Infections
Pseudomonas aeruginosa
Signal Transduction
Toll-Like Receptor 9
The retention of intracellular Toll-like receptors (TLRs) in the endoplasmic reticulum prevents their activation under basal conditions. TLR9 is activated by sensing ligands in specific endosomal-lysosomal compartments. Here we identified IRAP+ endosomes as major cellular compartments for the early steps of TLR9 activation in dendritic cells (DCs). Both TLR9 and its ligand, the dinucleotide CpG, were present as cargo in IRAP+ endosomes. In the absence of the aminopeptidase IRAP, the trafficking of CpG and TLR9 to lysosomes and signaling via TLR9 were enhanced in DCs and in mice following bacterial infection. IRAP stabilized CpG-containing endosomes by interacting with the actin-nucleation factor FHOD4, which slowed the trafficking of TLR9 toward lysosomes. Thus, endosomal retention of TLR9 via the interaction of IRAP with the actin cytoskeleton is a mechanism that prevents hyper-activation of TLR9 in DCs.
2018-01-08T11:50:07Z
2018-01-08T11:50:07Z
2017-05
Article
IRAP+ endosomes restrict TLR9 activation and signaling. 2017, 18 (5):509-518 Nat. Immunol.
1529-2916
28319098
10.1038/ni.3711
http://hdl.handle.net/10033/621226
Nature immunology
en
http://creativecommons.org/licenses/by-nc-sa/4.0/
oai:repository.helmholtz-hzi.de:10033/6227062021-01-28T01:39:39Zcom_10033_128109col_10033_620747
The Cytomegalovirus Tegument Protein UL35 Antagonizes Pattern Recognition Receptor-Mediated Type I IFN Transcription.
Fabits, Markus
Gonçalves Magalhães, Vladimir
Chan, Baca
Girault, Virginie
Elbasani, Endrit
Rossetti, Elisa
Saeland, Eirikur
Messerle, Martin
Pichlmair, Andreas
Lisnić, Vanda Juranić
Brinkmann, Melanie M
HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
herpesvirus, cytomegalovirus, pattern recognition receptor, cGAS, STING, RIG-I, TBK1, UL35, type I interferon, OGT
herpesvirus
cytomegalovirus
pattern recognition receptor
cGAS
STING
RIG-I
TBK1
The rapid activation of pattern recognition receptor (PRR)-mediated type I interferon (IFN) signaling is crucial for the host response to infection. In turn, human cytomegalovirus (HCMV) must evade this potent response to establish life-long infection. Here, we reveal that the HCMV tegument protein UL35 antagonizes the activation of type I IFN transcription downstream of the DNA and RNA sensors cGAS and RIG-I, respectively. We show that ectopic expression of UL35 diminishes the type I IFN response, while infection with a recombinant HCMV lacking UL35 induces an elevated type I IFN response compared to wildtype HCMV. With a series of luciferase reporter assays and the analysis of signaling kinetics upon HCMV infection, we observed that UL35 downmodulates PRR signaling at the level of the key signaling factor TANK-binding kinase 1 (TBK1). Finally, we demonstrate that UL35 and TBK1 co-immunoprecipitate when co-expressed in HEK293T cells. In addition, we show that a previously reported cellular binding partner of UL35, O-GlcNAc transferase (OGT), post-translationally GlcNAcylates UL35, but that this modification is not required for the antagonizing effect of UL35 on PRR signaling. In summary, we have identified UL35 as the first HCMV protein to antagonize the type I IFN response at the level of TBK1, thereby enriching our understanding of how this important herpesvirus escapes host immune responses.
2021-01-27T14:34:40Z
2021-01-27T14:34:40Z
2020-05-26
Article
Microorganisms. 2020 May 26;8(6):790. doi: 10.3390/microorganisms8060790.
2076-2607
32466380
10.3390/microorganisms8060790
http://hdl.handle.net/10033/622706
Microorganisms
en
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
MDPI
8
6
Microorganisms
Switzerland