Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes.

2.50
Hdl Handle:
http://hdl.handle.net/10033/92849
Title:
Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes.
Authors:
Stockinger, Silvia; Kastner, Renate; Kernbauer, Elisabeth; Pilz, Andreas; Westermayer, Sandra; Reutterer, Benjamin; Soulat, Didier; Stengl, Gabriele; Vogl, Claus; Frenz, Theresa; Waibler, Zoe; Taniguchi, Tadatsugu; Rülicke, Thomas; Kalinke, Ulrich ( 0000-0003-0503-9564 ) ; Müller, Mathias; Decker, Thomas
Abstract:
Production of type I interferons (IFN-I, mainly IFNalpha and IFNbeta) is a hallmark of innate immune responses to all classes of pathogens. When viral infection spreads to lymphoid organs, the majority of systemic IFN-I is produced by a specialized "interferon-producing cell" (IPC) that has been shown to belong to the lineage of plasmacytoid dendritic cells (pDC). It is unclear whether production of systemic IFN-I is generally attributable to pDC irrespective of the nature of the infecting pathogen. We have addressed this question by studying infections of mice with the intracellular bacterium Listeria monocytogenes. Protective innate immunity against this pathogen is weakened by IFN-I activity. In mice infected with L. monocytogenes, systemic IFN-I was amplified via IFN-beta, the IFN-I receptor (IFNAR), and transcription factor interferon regulatory factor 7 (IRF7), a molecular circuitry usually characteristic of non-pDC producers. Synthesis of serum IFN-I did not require TLR9. In contrast, in vitro-differentiated pDC infected with L. monocytogenes needed TLR9 to transcribe IFN-I mRNA. Consistent with the assumption that pDC are not the producers of systemic IFN-I, conditional ablation of the IFN-I receptor in mice showed that most systemic IFN-I is produced by myeloid cells. Furthermore, results obtained with FACS-purified splenic cell populations from infected mice confirmed the assumption that a cell type with surface antigens characteristic of macrophages and not of pDC is responsible for bulk IFN-I synthesis. The amount of IFN-I produced in the investigated mouse lines was inversely correlated to the resistance to lethal infection. Based on these data, we propose that the engagement of pDC, the mode of IFN-I mobilization, as well as the shaping of the antimicrobial innate immune response by IFN-I differ between intracellular pathogens.
Affiliation:
Max F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.
Citation:
Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. 2009, 5 (3):e1000355 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Mar-2009
URI:
http://hdl.handle.net/10033/92849
DOI:
10.1371/journal.ppat.1000355
PubMed ID:
19325882
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorStockinger, Silviaen
dc.contributor.authorKastner, Renateen
dc.contributor.authorKernbauer, Elisabethen
dc.contributor.authorPilz, Andreasen
dc.contributor.authorWestermayer, Sandraen
dc.contributor.authorReutterer, Benjaminen
dc.contributor.authorSoulat, Didieren
dc.contributor.authorStengl, Gabrieleen
dc.contributor.authorVogl, Clausen
dc.contributor.authorFrenz, Theresaen
dc.contributor.authorWaibler, Zoeen
dc.contributor.authorTaniguchi, Tadatsuguen
dc.contributor.authorRülicke, Thomasen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorMüller, Mathiasen
dc.contributor.authorDecker, Thomasen
dc.date.accessioned2010-02-24T12:22:05Zen
dc.date.available2010-02-24T12:22:05Zen
dc.date.issued2009-03en
dc.identifier.citationCharacterization of the interferon-producing cell in mice infected with Listeria monocytogenes. 2009, 5 (3):e1000355 PLoS Pathog.en
dc.identifier.issn1553-7374en
dc.identifier.pmid19325882en
dc.identifier.doi10.1371/journal.ppat.1000355en
dc.identifier.urihttp://hdl.handle.net/10033/92849en
dc.description.abstractProduction of type I interferons (IFN-I, mainly IFNalpha and IFNbeta) is a hallmark of innate immune responses to all classes of pathogens. When viral infection spreads to lymphoid organs, the majority of systemic IFN-I is produced by a specialized "interferon-producing cell" (IPC) that has been shown to belong to the lineage of plasmacytoid dendritic cells (pDC). It is unclear whether production of systemic IFN-I is generally attributable to pDC irrespective of the nature of the infecting pathogen. We have addressed this question by studying infections of mice with the intracellular bacterium Listeria monocytogenes. Protective innate immunity against this pathogen is weakened by IFN-I activity. In mice infected with L. monocytogenes, systemic IFN-I was amplified via IFN-beta, the IFN-I receptor (IFNAR), and transcription factor interferon regulatory factor 7 (IRF7), a molecular circuitry usually characteristic of non-pDC producers. Synthesis of serum IFN-I did not require TLR9. In contrast, in vitro-differentiated pDC infected with L. monocytogenes needed TLR9 to transcribe IFN-I mRNA. Consistent with the assumption that pDC are not the producers of systemic IFN-I, conditional ablation of the IFN-I receptor in mice showed that most systemic IFN-I is produced by myeloid cells. Furthermore, results obtained with FACS-purified splenic cell populations from infected mice confirmed the assumption that a cell type with surface antigens characteristic of macrophages and not of pDC is responsible for bulk IFN-I synthesis. The amount of IFN-I produced in the investigated mouse lines was inversely correlated to the resistance to lethal infection. Based on these data, we propose that the engagement of pDC, the mode of IFN-I mobilization, as well as the shaping of the antimicrobial innate immune response by IFN-I differ between intracellular pathogens.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshAntigens, CDen
dc.subject.meshDendritic Cellsen
dc.subject.meshFlow Cytometryen
dc.subject.meshInterferon Regulatory Factor-7en
dc.subject.meshInterferon Type Ien
dc.subject.meshInterferon-betaen
dc.subject.meshListeria Infectionsen
dc.subject.meshListeria monocytogenesen
dc.subject.meshMacrophagesen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred C57BLen
dc.subject.meshPhenotypeen
dc.subject.meshReverse Transcriptase Polymerase Chain Reactionen
dc.subject.meshSpleenen
dc.subject.meshToll-Like Receptor 9en
dc.titleCharacterization of the interferon-producing cell in mice infected with Listeria monocytogenes.en
dc.typeArticleen
dc.contributor.departmentMax F. Perutz Laboratories, Department of Microbiology and Immunobiology, University of Vienna, Vienna, Austria.en
dc.identifier.journalPLoS pathogensen

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