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-beta, 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.
Publication types
-
Comparative Study
-
Research Support, U.S. Gov't, Non-P.H.S.
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Adaptor Proteins, Signal Transducing
-
Adaptor Proteins, Vesicular Transport / physiology*
-
Adjuvants, Immunologic / pharmacology*
-
Animals
-
Antigens, CD / drug effects
-
Antigens, CD / immunology
-
Antigens, Differentiation / immunology
-
B7-1 Antigen / drug effects
-
B7-1 Antigen / immunology
-
B7-2 Antigen
-
CD40 Antigens / drug effects
-
CD40 Antigens / immunology
-
Immunity, Cellular / physiology*
-
Lipopolysaccharides / pharmacology
-
Macrophages / physiology
-
Membrane Glycoproteins / drug effects
-
Membrane Glycoproteins / immunology
-
Membrane Proteins
-
Mice
-
Molecular Sequence Data
-
Mutation
-
Myeloid Differentiation Factor 88
-
RNA, Double-Stranded / pharmacology
-
Receptor, Interferon alpha-beta
-
Receptors, Cell Surface / immunology
-
Receptors, Immunologic / immunology
-
Receptors, Interferon / immunology
-
Signal Transduction / immunology
-
Toll-Like Receptor 3
-
Toll-Like Receptor 4
-
Toll-Like Receptors
-
Up-Regulation
-
eIF-2 Kinase / immunology
Substances
-
Adaptor Proteins, Signal Transducing
-
Adaptor Proteins, Vesicular Transport
-
Adjuvants, Immunologic
-
Antigens, CD
-
Antigens, Differentiation
-
B7-1 Antigen
-
B7-2 Antigen
-
CD40 Antigens
-
Cd86 protein, mouse
-
Lipopolysaccharides
-
MYD88 protein, human
-
Membrane Glycoproteins
-
Membrane Proteins
-
Myd88 protein, mouse
-
Myeloid Differentiation Factor 88
-
RNA, Double-Stranded
-
Receptors, Cell Surface
-
Receptors, Immunologic
-
Receptors, Interferon
-
TICAM1 protein, human
-
Toll-Like Receptor 3
-
Toll-Like Receptor 4
-
Toll-Like Receptors
-
Receptor, Interferon alpha-beta
-
eIF-2 Kinase