Innate immune response to streptococcus pyogenes depends on the combined activation of TLR13 and TLR2

Christina Fieber, Marton Janos, Tina Koestler, Nina Gratz, Xiao Dong Li, Virginia Castiglia, Marion Aberle, Martina Sauert, Mareike Wegner, Lena Alexopoulou, Carsten J. Kirschning, Zhijian J. Chen, Arndt Von Haeseler, Pavel Kovarik

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Innate immune recognition of the major human-specific Gram-positive pathogen Streptococcus pyogenes is not understood. Here we show that mice employ Toll-like receptor (TLR) 2- and TLR13-mediated recognition of S. pyogenes. These TLR pathways are nonredundant in the in vivo context of animal infection, but are largely redundant in vitro, as only inactivation of both of them abolishes inflammatory cytokine production by macrophages and dendritic cells infected with S . pyogenes. Mechanistically, S. pyogenes is initially recognized in a phagocytosis-independent manner by TLR2 and subsequently by TLR13 upon internalization. We show that the TLR13 response is specifically triggered by S. pyogenes rRNA and that Tlr13-/-cells respond to S . pyogenes infection solely by engagement of TLR2. TLR13 is absent from humans and, remarkably, we find no equivalent route for S. pyogenes RNA recognition in human macrophages. Phylogenetic analysis reveals that TLR13 occurs in all kingdoms but only in few mammals, including mice and rats, which are naturally resistant against S. pyogenes. Our study establishes that the dissimilar expression of TLR13 in mice and humans has functional consequences for recognition of S. pyogenes in these organisms.

Original languageEnglish (US)
Article numbere0119727
JournalPloS one
Volume10
Issue number3
DOIs
StatePublished - Mar 10 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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