Viral infection augments Nod1/2 signaling to potentiate lethality associated with secondary bacterial infections

Yun Gi Kim, Jong Hwan Park, Thornik Reimer, Darren P. Baker, Taro Kawai, Himanshu Kumar, Shizuo Akira, Christiane Wobus, Gabriel Núñez

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

Secondary bacterial infection is a common sequela to viral infection and is associated with increased lethality and morbidity. However, the underlying mechanisms remain poorly understood. We show that the TLR3/MDA5 agonist poly I:C or viral infection dramatically augments signaling via the NLRs Nod1 and Nod2 and enhances the production of proinflammatory cytokines. Enhanced Nod1 and Nod2 signaling by poly I:C required the TLR3/MDA5 adaptors TRIF and IPS-1 and was mediated by type I IFNs. Mechanistically, poly I:C or IFN-β induced the expression of Nod1, Nod2, and the Nod-signaling adaptor Rip2. Systemic administration of poly I:C or IFN-β or infection with murine norovirus-1 promoted inflammation and lethality in mice superinfected with E. coli, which was independent of bacterial burden but attenuated in the absence of Nod1/Nod2 or Rip2. Thus, crosstalk between type I IFNs and Nod1/Nod2 signaling promotes bacterial recognition, but induces harmful effects in the virally infected host.

Original languageEnglish
Pages (from-to)496-507
Number of pages12
JournalCell Host and Microbe
Volume9
Issue number6
DOIs
Publication statusPublished - 2011 Jun 16
Externally publishedYes

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Kim, Y. G., Park, J. H., Reimer, T., Baker, D. P., Kawai, T., Kumar, H., Akira, S., Wobus, C., & Núñez, G. (2011). Viral infection augments Nod1/2 signaling to potentiate lethality associated with secondary bacterial infections. Cell Host and Microbe, 9(6), 496-507. https://doi.org/10.1016/j.chom.2011.05.006