Journal
BLOOD
Volume 118, Issue 10, Pages 2763-2773Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-02-339515
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Funding
- National Institutes of Health National Institute of Allergy and Infectious Diseases [R01 AI057029, R01 AI071852]
- Yerkes National Primate Research Center [P51 RR00165]
- Emory Continuing and Facilitating AIDS Research grant [P30 AI050409]
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In SIV/HIV infection, the gastrointestinal tissue dominates as an important site because of the impact of massive mucosal CD4 depletion and immune activation-induced tissue pathology. Unlike AIDS-susceptible rhesus macaques, natural hosts do not progress to AIDS and resolve immune activation earlier. Here, we examine the role of dendritic cells (DCs) in mediating immune activation and disease progression. We demonstrate that plasmacytoid DCs (pDCs) in the blood up-regulate beta 7-integrin and are rapidly recruited to the colorectum after a pathogenic SIV infection in rhesus macaques. These pDCs were capable of producing proinflammatory cytokines and primed a T cytotoxic 1 response in vitro. Consistent with the up-regulation of beta 7-integrin on pDCs, in vivo blockade of alpha 4 beta 7-integrin dampened pDC recruitment to the colorectum and resulted in reduced immune activation. The up-regulation of beta 7-integrin expression on pDCs in the blood also was observed in HIV-infected humans but not in chronically SIV-infected sooty mangabeys that show low levels of immune activation. Our results uncover a new mechanism by which pDCs influence immune activation in colorectal tissue after pathogenic immunodeficiency virus infections. (Blood. 2011;118(10):2763-2773)
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