Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes.
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 ha...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2009-03-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000355&type=printable |
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| author | Silvia Stockinger Renate Kastner Elisabeth Kernbauer Andreas Pilz Sandra Westermayer Benjamin Reutterer Didier Soulat Gabriele Stengl Claus Vogl Theresa Frenz Zoe Waibler Tadatsugu Taniguchi Thomas Rülicke Ulrich Kalinke Mathias Müller Thomas Decker |
| author_facet | Silvia Stockinger Renate Kastner Elisabeth Kernbauer Andreas Pilz Sandra Westermayer Benjamin Reutterer Didier Soulat Gabriele Stengl Claus Vogl Theresa Frenz Zoe Waibler Tadatsugu Taniguchi Thomas Rülicke Ulrich Kalinke Mathias Müller Thomas Decker |
| author_sort | Silvia Stockinger |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ea4b3e9c4ca1489194c4b1cd4a59160f |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2009-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-ea4b3e9c4ca1489194c4b1cd4a59160f2025-08-20T02:02:48ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742009-03-0153e100035510.1371/journal.ppat.1000355Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes.Silvia StockingerRenate KastnerElisabeth KernbauerAndreas PilzSandra WestermayerBenjamin ReuttererDidier SoulatGabriele StenglClaus VoglTheresa FrenzZoe WaiblerTadatsugu TaniguchiThomas RülickeUlrich KalinkeMathias MüllerThomas DeckerProduction 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.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000355&type=printable |
| spellingShingle | Silvia Stockinger Renate Kastner Elisabeth Kernbauer Andreas Pilz Sandra Westermayer Benjamin Reutterer Didier Soulat Gabriele Stengl Claus Vogl Theresa Frenz Zoe Waibler Tadatsugu Taniguchi Thomas Rülicke Ulrich Kalinke Mathias Müller Thomas Decker Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. PLoS Pathogens |
| title | Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. |
| title_full | Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. |
| title_fullStr | Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. |
| title_full_unstemmed | Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. |
| title_short | Characterization of the interferon-producing cell in mice infected with Listeria monocytogenes. |
| title_sort | characterization of the interferon producing cell in mice infected with listeria monocytogenes |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1000355&type=printable |
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