title: NLRX1 does not inhibit MAVS-dependent antiviral signalling.
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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Fraser
authors.initials: F
authors.lastname: Soares
authors.forename: Ivan
authors.initials: I
authors.lastname: Tattoli
authors.forename: Michael E
authors.initials: ME
authors.lastname: Wortzman
authors.forename: Damien
authors.initials: D
authors.lastname: Arnoult
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Philpott
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D054357:Chemokine CXCL10 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology*; D007113:Immunity, Innate; D018836:Inflammation Mediators / Q000378:metabolism; D009980:Influenza A virus / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D011070:Poly I-C / Q000276:immunology; D010253:Respirovirus Infections / Q000276:immunology*; D029082:Sendai virus / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054357:Chemokine CXCL10; D018836:Inflammation Mediators; D015850:Interleukin-6; D024101:Mitochondrial Proteins; D011070:Poly I-C; C512612:MAVS protein, mouse; C555655:NLRX1 protein, mouse