SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection

Ying Ju Hou, Rebecca Banerjee, Bobby Thomas, Carl Nathan, Adolfo Garciá-Sastre, Aihao Ding, Melissa B. Uccellini

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)875-883
Number of pages9
JournalJournal of Immunology
Volume191
Issue number2
DOIs
StatePublished - Jul 15 2013

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Central Nervous System Viral Diseases
Innate Immunity
Cytokines
Wounds and Injuries
Vesicular Stomatitis
Caenorhabditis elegans
Listeria monocytogenes
Microglia
Orthomyxoviridae
Mycobacterium tuberculosis
Viruses
Neurons
Infection

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hou, Y. J., Banerjee, R., Thomas, B., Nathan, C., Garciá-Sastre, A., Ding, A., & Uccellini, M. B. (2013). SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection. Journal of Immunology, 191(2), 875-883. https://doi.org/10.4049/jimmunol.1300374

SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection. / Hou, Ying Ju; Banerjee, Rebecca; Thomas, Bobby; Nathan, Carl; Garciá-Sastre, Adolfo; Ding, Aihao; Uccellini, Melissa B.

In: Journal of Immunology, Vol. 191, No. 2, 15.07.2013, p. 875-883.

Research output: Contribution to journalArticle

Hou, YJ, Banerjee, R, Thomas, B, Nathan, C, Garciá-Sastre, A, Ding, A & Uccellini, MB 2013, 'SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection', Journal of Immunology, vol. 191, no. 2, pp. 875-883. https://doi.org/10.4049/jimmunol.1300374
Hou, Ying Ju ; Banerjee, Rebecca ; Thomas, Bobby ; Nathan, Carl ; Garciá-Sastre, Adolfo ; Ding, Aihao ; Uccellini, Melissa B. / SARM is required for neuronal injury and cytokine production in response to central nervous system viral infection. In: Journal of Immunology. 2013 ; Vol. 191, No. 2. pp. 875-883.
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