DAP12 (KARAP) amplifies inflammation and increases mortality from endotoxemia and septic peritonitis

Isaiah R. Turnbull, Jonathan E. McDunn, Toshiyuki Takai, R. Reid Townsend, J. Perren Cobb, Marco Colonna

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

DAP12 (KARAP) is a transmembrane signaling adaptor for a family of innate immunoreceptors that have been shown to activate granulocytes and monocytes/macrophages, amplifying production of inflammatory cytokines. Contrasting with these data, recent studies suggest that DAP12 signaling has an inhibitory role in the macrophage response to microbial products (Hamerman, J.A., N.K. Tchao, C.A. Lowell, and L.L. Lanier. 2005. Nat. Immunol. 6:579-586). To determine the in vivo role for DAP12 signaling in inflammation, we measured the response of wild-type (WT) and DAP12-/- mice to septic shock. We show that DAP12-/- mice have improved survival from both endotoxemia and cecal ligation and puncture-induced septic shock. As compared with WT mice, DAP12-/- mice have decreased plasma cytokine levels and a decreased acute phase response during sepsis, but no defect in the recruitment of cells or bacterial control. In cells isolated after sepsis and stimulated ex vivo, DAP12 signaling augments lipopolysaccharide-mediated cytokine production. These data demonstrate that, during sepsis, DAP12 signaling augments the response to microbial products, amplifying inflammation and contributing to mortality. JEM

Original languageEnglish
Pages (from-to)363-369
Number of pages7
JournalJournal of Experimental Medicine
Volume202
Issue number3
DOIs
Publication statusPublished - 2005 Aug 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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