Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways

Kasper Hoebe, Edith M. Janssen, Sung O. Kim, Lena Alexopoulou, Richard A. Flavell, Jiahuai Han, Bruce Beutler

Research output: Contribution to journalArticle

362 Scopus citations

Abstract

Both lipopolysaccharide (LPS) and double-stranded RNA (dsRNA) are adjuvants for the adaptive immune response, inducing upregulation of costimulatory molecules (UCM) on antigen-presenting cells. Trif, an adapter protein that transduces signals from Toll-like receptor 4 (TLR4) and TLR3, permits the induction of many cytokines, including interferon-β, which signals through the type I interferon receptor. We show here that LPS-induced UCM was strictly dependent on the TLR4→Trif axis, whereas dsRNA-induced UCM was only partly dependent on the TLR3→Trif axis. But both LPS-and dsRNA-induced UCM were entirely dependent on type I interferon receptor signaling. These findings show that UCM involves an autocrine or paracrine loop, and indicate that an alternative TLR3-independent, Trif-independent pathway contributes to dsRNA-induced UCM.

Original languageEnglish (US)
Pages (from-to)1223-1229
Number of pages7
JournalNature immunology
Volume4
Issue number12
DOIs
StatePublished - Dec 1 2003

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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