期刊
MUCOSAL IMMUNOLOGY
卷 4, 期 5, 页码 528-538出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mi.2011.1
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资金
- National Institutes of Health/National Institute of Allergy and Infectious Diseases [R01 AI057029, R01 AI071852, U54 AI057157, R37 AI48638, R01 DK057665]
- Yerkes National Primate Research Center [P51 RR00165]
- Emory CFAR [P30 AI050409]
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-kappa B 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.
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