A Subset of Toll-Like Receptor Ligands Induces Cross-presentation by Bone Marrow-Derived Dendritic Cells

• Published in: The Journal of immunology (1950) 2003-04, Vol.170 (8), p.4102-4110
• Main Authors: Datta, Sandip K, Redecke, Vanessa, Prilliman, Kiley R, Takabayashi, Kenji, Corr, Maripat, Tallant, Thomas, DiDonato, Joseph, Dziarski, Roman, Akira, Shizuo, Schoenberger, Stephen P, Raz, Eyal
• Format: Article
• Language: English
• Subjects: 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
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.170.8.4102

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.