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* Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, La Jolla, CA 92093;
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121;
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195;
Department of Microbiology and Immunology, Northwest Center for Medical Education, Indiana University, Gary, IN 46408; and
¶ Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
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.
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