title: Adenovirus type 5 induces vitamin A-metabolizing enzymes in dendritic cells and enhances priming of gut-homing CD8 T cells.
abstract: Protective immunity at the gut-associated mucosal tissue is induced primarily by oral/rectal immunization owing to the need for targeting antigen to the gut-resident dendritic cells (DCs). In this study we show that an adenovirus type 5 (Ad5)-based human immunodeficiency virus type 1 vaccine can prime a durable antigen-specific CD8 T-cell response in the gut following intramuscular (IM) immunization in mice. The ability of Ad5 to prime gut-homing CD8 T cells in vivo was associated with Ad5-induced expression of retinal dehydrogenase (RALDH) enzymes in conventional DCs. The Ad5-mediated induction of RALDH did not require signaling through Toll-like receptors, DNA-dependent activator of interferon regulatory factors and several mitogen-activated protein kinases, or replication capacity of the virus, but was dependent on nuclear factor-κB and granulocyte-macrophage colony-stimulating factor. These results provide an innate mechanism through which Ad5-stimulated DCs prime gut-homing CD8 T cells and have implications for the development of novel mucosal adjuvants for subunit vaccines administered via the IM route.
authors.affiliation: Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ganguly
authors.forename: S
authors.initials: S
authors.lastname: Manicassamy
authors.forename: J
authors.initials: J
authors.lastname: Blackwell
authors.forename: B
authors.initials: B
authors.lastname: Pulendran
authors.forename: R R
authors.initials: RR
authors.lastname: Amara
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology; D000256:Adenoviridae / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000201:enzymology* / Q000276:immunology* / Q000821:virology; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013154:Spleen / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D016915:AIDS Vaccines; D016328:NF-kappa B; D014212:Tretinoin; D050697:Retinal Dehydrogenase; D058570:TOR Serine-Threonine Kinases