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.
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Supported by funding from the National Institutes of Health and by the Defense Advanced Research Projects Agency.
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Hoebe, K., Janssen, E., Kim, S. et al. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol 4, 1223–1229 (2003). https://doi.org/10.1038/ni1010
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DOI: https://doi.org/10.1038/ni1010