Plasmacytoid dendritic cells are recruited to the colorectum and contribute to immune activation during pathogenic SIV infection in rhesus macaques

被引:84
作者
Kwa, Suefen [1 ]
Kannanganat, Sunil [1 ]
Nigam, Pragati [1 ]
Siddiqui, Mariam [1 ]
Shetty, Ravi Dyavar [1 ]
Armstrong, Wendy [2 ]
Ansari, Aftab [3 ]
Bosinger, Steven E. [1 ]
Silvestri, Guido [1 ]
Amara, Rama Rao [1 ]
机构
[1] Emory Univ, Emory Vaccine Ctr, Dept Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30329 USA
[2] Emory Univ, Dept Infect Dis, Emory Univ Sch Med, Atlanta, GA 30329 USA
[3] Emory Univ, Dept Pathol & Lab Med, Emory Univ Sch Med, Atlanta, GA 30329 USA
基金
美国国家卫生研究院;
关键词
SIMIAN IMMUNODEFICIENCY VIRUS; CD4(+) T-CELLS; AFRICAN-GREEN MONKEYS; SOOTY MANGABEYS; I INTERFERON; GENE-EXPRESSION; LYMPH-NODES; ANTIRETROVIRAL THERAPY; GASTROINTESTINAL-TRACT; COLLAGEN DEPOSITION;
D O I
10.1182/blood-2011-02-339515
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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)
引用
收藏
页码:2763 / 2773
页数:11
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