Abstract
Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8(+) CTLs. Detection of microbial products by Toll-like receptors (TLRs) leads to activation of DCs and subsequent orchestration of an adaptive immune response. We hypothesized that microbial TLR ligands could activate DCs to cross-present Ag to CTLs. Using DCs and CTLs in an in vitro cross-presentation system, we show that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast to presentation of Ag to CD4(+) T cells by immature DCs, TLR-induced cross-presentation is mediated by mature DCs, is independent of endosomal acidification, and relies on cytosolic Ag processing machinery.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic / physiology
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Animals
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Antigen Presentation / immunology*
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Antigens, Bacterial / immunology
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Antigens, Bacterial / metabolism
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Antigens, Differentiation / physiology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology*
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Bone Marrow Cells / metabolism*
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Cell Differentiation / immunology
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Cells, Cultured
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CpG Islands / immunology
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Cytosol / immunology
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Cytosol / metabolism
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Dendritic Cells / cytology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism*
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Down-Regulation / immunology
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Flagellin / immunology
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Flagellin / metabolism
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Histocompatibility Antigens Class I / immunology
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Histocompatibility Antigens Class I / metabolism
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Histocompatibility Antigens Class II / immunology
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Histocompatibility Antigens Class II / metabolism
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Intracellular Fluid / immunology
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Intracellular Fluid / metabolism
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Ligands
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Lipopolysaccharides / immunology
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Lipopolysaccharides / metabolism
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Male
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Membrane Glycoproteins / biosynthesis
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Membrane Glycoproteins / metabolism*
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Myeloid Differentiation Factor 88
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Peptidoglycan / immunology
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Peptidoglycan / metabolism
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Poly I-C / immunology
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Poly I-C / metabolism
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Receptors, Cell Surface / biosynthesis
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Receptors, Cell Surface / metabolism*
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Receptors, Cell Surface / physiology
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Receptors, Immunologic / physiology
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Toll-Like Receptor 3
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Toll-Like Receptors
Substances
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Adaptor Proteins, Signal Transducing
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Adjuvants, Immunologic
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Antigens, Bacterial
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Antigens, Differentiation
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Histocompatibility Antigens Class I
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Histocompatibility Antigens Class II
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Ligands
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Lipopolysaccharides
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Membrane Glycoproteins
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Myd88 protein, mouse
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Myeloid Differentiation Factor 88
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Peptidoglycan
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Receptors, Cell Surface
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Receptors, Immunologic
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Toll-Like Receptor 3
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Toll-Like Receptors
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Flagellin
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Poly I-C