Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection.
Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-05-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001345&type=printable |
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| author | Nina Gratz Harald Hartweger Ulrich Matt Franz Kratochvill Marton Janos Stefanie Sigel Barbara Drobits Xiao-Dong Li Sylvia Knapp Pavel Kovarik |
| author_facet | Nina Gratz Harald Hartweger Ulrich Matt Franz Kratochvill Marton Janos Stefanie Sigel Barbara Drobits Xiao-Dong Li Sylvia Knapp Pavel Kovarik |
| author_sort | Nina Gratz |
| collection | DOAJ |
| description | Streptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection. Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different signaling pathways leading to IFN-beta production. Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88. Furthermore, IFN-beta production by macrophages was dependent on the endosomal delivery of streptococcal DNA, while in cDCs streptococcal RNA was identified as the IFN-beta inducer. Despite a role of MyD88 in both cell types, the known IFN-inducing TLRs were individually not required for generation of the IFN-beta response. These results demonstrate that the innate immune system employs several strategies to efficiently recognize S. pyogenes, a pathogenic bacterium that succeeded in avoiding recognition by the standard arsenal of TLRs. |
| format | Article |
| id | doaj-art-36a18e2ee4db4801a63462a80f600521 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2011-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-36a18e2ee4db4801a63462a80f6005212025-08-20T02:08:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742011-05-0175e100134510.1371/journal.ppat.1001345Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection.Nina GratzHarald HartwegerUlrich MattFranz KratochvillMarton JanosStefanie SigelBarbara DrobitsXiao-Dong LiSylvia KnappPavel KovarikStreptococcus pyogenes is a Gram-positive human pathogen that is recognized by yet unknown pattern recognition receptors (PRRs). Engagement of these receptor molecules during infection with S. pyogenes, a largely extracellular bacterium with limited capacity for intracellular survival, causes innate immune cells to produce inflammatory mediators such as TNF, but also type I interferon (IFN). Here we show that signaling elicited by type I IFNs is required for successful defense of mice against lethal subcutaneous cellulitis caused by S. pyogenes. Type I IFN signaling was accompanied with reduced neutrophil recruitment to the site of infection. Mechanistic analysis revealed that macrophages and conventional dendritic cells (cDCs) employ different signaling pathways leading to IFN-beta production. Macrophages required IRF3, STING, TBK1 and partially MyD88, whereas in cDCs the IFN-beta production was fully dependent on IRF5 and MyD88. Furthermore, IFN-beta production by macrophages was dependent on the endosomal delivery of streptococcal DNA, while in cDCs streptococcal RNA was identified as the IFN-beta inducer. Despite a role of MyD88 in both cell types, the known IFN-inducing TLRs were individually not required for generation of the IFN-beta response. These results demonstrate that the innate immune system employs several strategies to efficiently recognize S. pyogenes, a pathogenic bacterium that succeeded in avoiding recognition by the standard arsenal of TLRs.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001345&type=printable |
| spellingShingle | Nina Gratz Harald Hartweger Ulrich Matt Franz Kratochvill Marton Janos Stefanie Sigel Barbara Drobits Xiao-Dong Li Sylvia Knapp Pavel Kovarik Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. PLoS Pathogens |
| title | Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. |
| title_full | Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. |
| title_fullStr | Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. |
| title_full_unstemmed | Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. |
| title_short | Type I interferon production induced by Streptococcus pyogenes-derived nucleic acids is required for host protection. |
| title_sort | type i interferon production induced by streptococcus pyogenes derived nucleic acids is required for host protection |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001345&type=printable |
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