A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells

J Immunol. 2003 Apr 15;170(8):4102-10. doi: 10.4049/jimmunol.170.8.4102.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adjuvants, Immunologic / physiology
  • Animals
  • Antigen Presentation / immunology*
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • Antigens, Differentiation / physiology
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / immunology*
  • Bone Marrow Cells / metabolism*
  • Cell Differentiation / immunology
  • Cells, Cultured
  • CpG Islands / immunology
  • Cytosol / immunology
  • Cytosol / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism*
  • Down-Regulation / immunology
  • Flagellin / immunology
  • Flagellin / metabolism
  • Histocompatibility Antigens Class I / immunology
  • Histocompatibility Antigens Class I / metabolism
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism
  • Intracellular Fluid / immunology
  • Intracellular Fluid / metabolism
  • Ligands
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / metabolism
  • Male
  • Membrane Glycoproteins / biosynthesis
  • Membrane Glycoproteins / metabolism*
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Myeloid Differentiation Factor 88
  • Peptidoglycan / immunology
  • Peptidoglycan / metabolism
  • Poly I-C / immunology
  • Poly I-C / metabolism
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / metabolism*
  • Receptors, Cell Surface / physiology
  • Receptors, Immunologic / physiology
  • Toll-Like Receptor 3
  • Toll-Like Receptors

Substances

  • Adaptor Proteins, Signal Transducing
  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • Antigens, Differentiation
  • Histocompatibility Antigens Class I
  • Histocompatibility Antigens Class II
  • Ligands
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Peptidoglycan
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Toll-Like Receptor 3
  • Toll-Like Receptors
  • Flagellin
  • Poly I-C