Adenovirus type 5 induces vitamin A-metabolizing enzymes in dendritic cells and enhances priming of gut-homing CD8 T cells

S. Ganguly, S. Manicassamy, J. Blackwell, B. Pulendran, R. R. Amara

Research output: Contribution to journalArticle

19 Scopus citations

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-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.

Original languageEnglish (US)
Pages (from-to)528-538
Number of pages11
JournalMucosal Immunology
Volume4
Issue number5
DOIs
Publication statusPublished - Sep 1 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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