title: A subset of Toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells.
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.
authors.affiliation: Department of Medicine and The Sam and Rose Stein Institute for Research on Aging, University of California, La Jolla, CA 92093, USA.
authors.forename: Sandip K
authors.initials: SK
authors.lastname: Datta
authors.forename: Vanessa
authors.initials: V
authors.lastname: Redecke
authors.forename: Kiley R
authors.initials: KR
authors.lastname: Prilliman
authors.forename: Kenji
authors.initials: K
authors.lastname: Takabayashi
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.forename: Thomas
authors.initials: T
authors.lastname: Tallant
authors.forename: Joseph
authors.initials: J
authors.lastname: DiDonato
authors.forename: Roman
authors.initials: R
authors.lastname: Dziarski
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Schoenberger
authors.forename: Eyal
authors.initials: E
authors.lastname: Raz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology; D005408:Flagellin / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan / Q000276:immunology / Q000378:metabolism; D011070:Poly I-C / Q000276:immunology / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000378:metabolism* / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D000943:Antigens, Differentiation; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D005408:Flagellin; D011070:Poly I-C