NLRX1 does not inhibit MAVS-dependent antiviral signalling

Innate Immun. 2013;19(4):438-48. doi: 10.1177/1753425912467383. Epub 2012 Dec 4.

Abstract

NLRX1 is a member of the Nod-like receptor family of intracellular sensors of microbial- and danger-associated molecular patterns. NLRX1 has a N-terminal mitochondrial addressing sequence that localizes the protein to the mitochondrial matrix. Recently, conflicting reports have been presented with regard to the putative implication of NLRX1 as a negative regulator of MAVS-dependent cytosolic antiviral responses. Here, we generated a new NLRX1 knockout mouse strain and observed that bone marrow-derived macrophages and murine embryonic fibroblasts from NLRX1-deficient mice displayed normal antiviral and inflammatory responses following Sendai virus infection. Importantly, wild type and NLRX1-deficient mice exhibited unaltered antiviral and inflammatory gene expression following intranasal challenge with influenza A virus or i.p. injection of Poly (I:C). Together, our results demonstrate that NLRX1 does not participate in the negative regulation of MAVS-dependent antiviral responses.

Keywords: MAVS; NLRX1; Nod-like receptors; RIG-I like receptors; innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Cell Line
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism
  • Fibroblasts / immunology*
  • Immunity, Innate
  • Inflammation Mediators / metabolism
  • Influenza A virus / immunology*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Orthomyxoviridae Infections / immunology*
  • Poly I-C / immunology
  • Respirovirus Infections / immunology*
  • Sendai virus / immunology*
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • Chemokine CXCL10
  • IPS-1 protein, mouse
  • Inflammation Mediators
  • Interleukin-6
  • Mitochondrial Proteins
  • NLRX1 protein, mouse
  • Poly I-C