[HTML][HTML] Type I Interferon Production Induced by Streptococcus pyogenes-Derived Nucleic Acids Is Required for Host Protection

N Gratz, H Hartweger, U Matt, F Kratochvill… - PLoS …, 2011 - journals.plos.org
N Gratz, H Hartweger, U Matt, F Kratochvill, M Janos, S Sigel, B Drobits, XD Li, S Knapp
PLoS pathogens, 2011journals.plos.org
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 …
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.
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