title: SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection.
abstract: Four of the five members of the Toll/IL-1R domain-containing adaptor family are required for signaling downstream of TLRs, promoting innate immune responses against different pathogens. However, the role of the fifth member of this family, sterile α and Toll/IL-1R domain-containing 1 (SARM), is unclear. SARM is expressed primarily in the CNS where it is required for axonal death. Studies in Caenorhabditis elegans have also shown a role for SARM in innate immunity. To clarify the role of mammalian SARM in innate immunity, we infected SARM(-/-) mice with a number of bacterial and viral pathogens. SARM(-/-) mice show normal responses to Listeria monocytogenes, Mycobacterium tuberculosis, and influenza virus, but show dramatic protection from death after CNS infection with vesicular stomatitis virus. Protection correlates with reduced CNS injury and cytokine production by nonhematopoietic cells, suggesting that SARM is a positive regulator of cytokine production. Neurons and microglia are the predominant source of cytokines in vivo, supporting a role for SARM as a link between neuronal injury and innate immunity.
authors.affiliation: Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Hou
authors.forename: Rebecca
authors.initials: R
authors.lastname: Banerjee
authors.forename: Bobby
authors.initials: B
authors.lastname: Thomas
authors.forename: Carl
authors.initials: C
authors.lastname: Nathan
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: Aihao
authors.initials: A
authors.lastname: Ding
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Uccellini
mesh_terms: D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D020805:Central Nervous System Viral Diseases / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology; D009474:Neurons / Q000378:metabolism; D018353:Rhabdoviridae Infections / Q000276:immunology* / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D051186:Armadillo Domain Proteins; D016207:Cytokines; D003598:Cytoskeletal Proteins; C543961:SARM1 protein, mouse