{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T16:29:02Z","timestamp":1780504142120,"version":"3.54.1"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2013,7,1]],"date-time":"2013-07-01T00:00:00Z","timestamp":1372636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Four of the five members of the Toll\/IL-1R domain\u2013containing 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 \u03b1 and Toll\/IL-1R domain\u2013containing 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\u2212\/\u2212 mice with a number of bacterial and viral pathogens. SARM\u2212\/\u2212 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1300374","type":"journal-article","created":{"date-parts":[[2013,6,8]],"date-time":"2013-06-08T02:02:38Z","timestamp":1370656958000},"page":"875-883","source":"Crossref","is-referenced-by-count":56,"title":["SARM Is Required for Neuronal Injury and Cytokine Production in Response to Central Nervous System Viral Infection"],"prefix":"10.1093","volume":"191","author":[{"given":"Ying-Ju","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neuroscience, Weill Medical College of Cornell University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bobby","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Georgia Health Sciences University Medical College of Georgia , Augusta, GA 30912"},{"name":"Department of Neurology, Georgia Health Sciences University Medical College of Georgia , Augusta, GA 30912"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Nathan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adolfo","family":"Garc\u00eda-Sastre","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"},{"name":"Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai , New York, NY 10029"},{"name":"Global Health and Emergent Pathogens Institute, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aihao","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University , New York, NY 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa B","family":"Uccellini","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Icahn School of Medicine at Mount Sinai , New York, NY 10029"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,7,15]]},"reference":[{"key":"2025032405081073300_r1","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling","volume":"7","author":"O\u2019Neill","year":"2007","journal-title":"Nat. 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Immunol."},{"key":"2025032405081073300_r24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.jneuroim.2010.05.034","article-title":"Distinct macrophage subpopulations regulate viral encephalitis but not viral clearance in the CNS","volume":"226","author":"Steel","year":"2010","journal-title":"J. Neuroimmunol."},{"key":"2025032405081073300_r25","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1097\/00005072-199810000-00004","article-title":"Expression of JE (monocyte chemoattractant protein-1) is induced by sciatic axotomy in wild type rodents but not in C57BL\/Wld(s) mice","volume":"57","author":"Carroll","year":"1998","journal-title":"J. Neuropathol. Exp. 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Dis."},{"key":"2025032405081073300_r33","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0301-0082(02)00127-2","article-title":"An inflammatory review of Parkinson\u2019s disease","volume":"68","author":"Orr","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"2025032405081073300_r34","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/1742-2094-5-50","article-title":"Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection","volume":"5","author":"Ovanesov","year":"2008","journal-title":"J. Neuroinflammation"},{"key":"2025032405081073300_r35","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1099\/vir.0.013565-0","article-title":"Glial activation involvement in neuronal death by Japanese encephalitis virus infection","volume":"91","author":"Chen","year":"2010","journal-title":"J. Gen. Virol."},{"key":"2025032405081073300_r36","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.virol.2010.01.025","article-title":"Vesicular stomatitis virus infects resident cells of the central nervous system and induces replication-dependent inflammatory responses","volume":"400","author":"Chauhan","year":"2010","journal-title":"Virology"},{"key":"2025032405081073300_r37","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nm.2399","article-title":"The immunology of stroke: from mechanisms to translation","volume":"17","author":"Iadecola","year":"2011","journal-title":"Nat. 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Neurosci."},{"key":"2025032405081073300_r41","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1111\/j.1750-3639.2010.00445.x","article-title":"Neuronal MCP-1 mediates microglia recruitment and neurodegeneration induced by the mild impairment of oxidative metabolism","volume":"21","author":"Yang","year":"2011","journal-title":"Brain Pathol."},{"key":"2025032405081073300_r42","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.mcn.2010.09.001","article-title":"TNF-\u03b1 potentiates glutamate-induced spinal cord motoneuron death via NF-\u03baB","volume":"46","author":"Tolosa","year":"2011","journal-title":"Mol. Cell. Neurosci."},{"key":"2025032405081073300_r43","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1006\/brbi.1995.1033","article-title":"Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors","volume":"9","author":"Chao","year":"1995","journal-title":"Brain Behav. Immun."},{"key":"2025032405081073300_r44","doi-asserted-by":"crossref","first-page":"6480","DOI":"10.1523\/JNEUROSCI.21-17-06480.2001","article-title":"Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity","volume":"21","author":"Bal-Price","year":"2001","journal-title":"J. Neurosci."},{"key":"2025032405081073300_r45","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/glia.22282","article-title":"Glutamate released by Japanese encephalitis virus-infected microglia involves TNF-\u03b1 signaling and contributes to neuronal death","volume":"60","author":"Chen","year":"2012","journal-title":"Glia"},{"key":"2025032405081073300_r46","doi-asserted-by":"crossref","first-page":"E197","DOI":"10.1073\/pnas.1111098109","article-title":"Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission","volume":"109","author":"Pascual","year":"2012","journal-title":"Proc. Natl. Acad. Sci. 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