Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection.
In: PLoS Pathogens, Jg. 7 (2011-05-01), Heft 5, S. 1-16
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Zugriff:
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. [ABSTRACT FROM AUTHOR]
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Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection.
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Autor/in / Beteiligte Person: | Gratz, Nina ; Hartweger, Harald ; Matt, Ulrich ; Kratochvill, Franz ; Janos, Marton ; Sigel, Stefanie ; Drobits, Barbara ; Li, Xiao-Dong ; Knapp, Sylvia ; Kovarik, Pavel |
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Zeitschrift: | PLoS Pathogens, Jg. 7 (2011-05-01), Heft 5, S. 1-16 |
Veröffentlichung: | 2011 |
Medientyp: | academicJournal |
ISSN: | 1553-7366 (print) |
DOI: | 10.1371/journal.ppat.1001345 |
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