Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses

Hideo Negishi, Hideyuki Yanai, Akira Nakajima, Ryuji Koshiba, Koji Atarashi, Atsushi Matsuda, Kosuke Matsuki, Shoji Miki, Takahiro Doi, Alan Aderem, Junko Nishio, Stephen T. Smale, Kenya Honda, Tadatsugu Taniguchi

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Although the mechanisms by which innate pathogen-recognition receptors enhance adaptive immune responses are increasingly well understood, whether signaling events from distinct classes of receptors affect each other in modulating adaptive immunity remains unclear. We found here that the activation of cytosolic RIG-I-like receptors (RLRs) resulted in the selective suppression of transcription of the gene encoding the p40 subunit of interleukin 12 (Il12b) that was effectively induced by the activation of Toll-like receptors (TLRs). The RLR-activated transcription factor IRF3 bound dominantly, relative to IRF5, to the Il12b promoter, where it interfered with the TLR-induced assembly of a productive transcription-factor complex. The activation of RLRs in mice attenuated TLR-induced responses of the T helper type 1 cell (T H1 cell) and interleukin 17-producing helper T cell (T H17 cell) subset types and, consequently, viral infection of mice caused death at sublethal doses of bacterial infection. The innate immune receptor cross-interference we describe may have implications for infection-associated clinical episodes.

Original languageEnglish
Pages (from-to)659-666
Number of pages8
JournalNature Immunology
Volume13
Issue number7
DOIs
Publication statusPublished - 2012 Jul

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Negishi, H., Yanai, H., Nakajima, A., Koshiba, R., Atarashi, K., Matsuda, A., Matsuki, K., Miki, S., Doi, T., Aderem, A., Nishio, J., Smale, S. T., Honda, K., & Taniguchi, T. (2012). Cross-interference of RLR and TLR signaling pathways modulates antibacterial T cell responses. Nature Immunology, 13(7), 659-666. https://doi.org/10.1038/ni.2307