An anti-inflammatory nod-like receptor is required for microglia development

Celia E. Shiau, Kelly Monk, William Joo, William S. Talbot

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Microglia are phagocytic cells that form the basis of the brain@s immune system. They derive from primitive macrophages that migrate into the brain during embryogenesis, but the genetic control of microglial development remains elusive. Starting with a genetic screen in zebrafish, we show that the noncanonical NOD-like receptor (NLR) nlrc3-like is essential for microglial formation. Although most NLRs trigger inflammatory signaling, nlrc3-like acts cell autonomously in microglia precursor cells to suppress unwarranted inflammation in the absence of overt immune challenge. In nlrc3-like mutants, primitive macrophages initiate a systemic inflammatory response with increased proinflammatory cytokines and actively aggregate instead of migrating into thebrain to form microglia. NLRC3-like requires both its pyrin and NACHT domains, and it can bind the inflammasome component apoptosis-associated speck-like protein. Our studies suggest that NLRC3-like may regulate the inflammasome and other inflammatory pathways. Together, these results demonstrate that NLRC3-like prevents inappropriate macrophage activation, thereby allowing normal microglial development.

Original languageEnglish (US)
Pages (from-to)1342-1352
Number of pages11
JournalCell Reports
Volume5
Issue number5
DOIs
Publication statusPublished - Dec 12 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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