Nature Immunology4, 1223 - 1229 (2003)
Published online: 16 November 2003; | doi:10.1038/ni1010
Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways
Kasper Hoebe1, Edith M Janssen2, Sung O Kim1, Lena Alexopoulou3, Richard A Flavell3, Jiahuai Han1
& Bruce Beutler1
1
The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
2
Division of Cellular Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA.
3
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Correspondence should be addressed to Bruce Beutler bruce@scripps.edu
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-, which signals through the type I interferon receptor. We show here that LPS-induced UCM was strictly dependent on the TLR4Trif axis, whereas dsRNA-induced UCM was only partly dependent on the TLR3Trif 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.
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, 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
B activation
