Adenovirus Type 5 Induces Vitamin A–Metabolizing Enzymes in Dendritic Cells and Enhances Priming of Gut Homing CD8 T Cells

• Type of Material: Article
• Authors: Sumita Ganguly, Emory University; Santhakumar Manicassamy, Emory University; Rama Rao Amara, Emory University
• Language: English
• Date: 2011-09
• Publisher: Nature Publishing Group
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011, Rights Managed by Nature Publishing Group
• Final Published Version (URL): http://www.nature.com/mi/journal/v4/n5/full/mi20111a.html
• Title of Journal or Parent Work: Mucosal Immunology
• ISSN: 1933-0219
• Volume: 4
• Issue: 5
• Start Page: 528
• End Page: 538
• Grant/Funding Information: This work was supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases grants R01 AI057029 and R01 AI071852 to RRA; Yerkes National Primate Research Center base grant, P51 RR00165; Emory CFAR grant P30 AI050409.
• Research Categories: Health Sciences, Immunology; Biology, Microbiology

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 (DC). Here we show that an adenovirus type 5 (Ad5) based HIV-1 vaccine can prime a durable antigen-specific CD8 T cell response in the gut following intramuscular 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 DC. The Ad5-mediated induction of RALDH did not require signaling through toll-like receptors, DNA-dependent activator of IRFs and several MAP kinases, or replication capacity of the virus, but was dependant on NF-κB and granulocyte-macrophage colony-stimulating factor. These results provide an innate mechanism through which Ad5-stimulated DC prime gut homing CD8 T cells and have implications for the development of novel mucosal adjuvants for subunit vaccines administered via the intramuscular route.