Type I Interferon Production Induced By Streptococcus Pyogenes-Derived Nucleic Acids is Required for Host Protection

Nina Gratz, Harald Hartweger, Ulrich Matt, Franz Kratochvill, Marton Janos, Stefanie Sigel, Barbara Drobits, Xiao Dong Li, Sylvia Knapp, Pavel Kovarik

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere1001345
JournalPLoS Pathogens
Volume7
Issue number5
DOIs
StatePublished - May 2011
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Gratz, N., Hartweger, H., Matt, U., Kratochvill, F., Janos, M., Sigel, S., Drobits, B., Li, X. D., Knapp, S., & Kovarik, P. (2011). Type I Interferon Production Induced By Streptococcus Pyogenes-Derived Nucleic Acids is Required for Host Protection. PLoS Pathogens, 7(5), [e1001345]. https://doi.org/10.1371/journal.ppat.1001345