Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: a model for HIV immunopathogenesis

被引：41

作者：

Boasso, Adriano ^{[1
]}

Royle, Caroline M. ^{[1
]}

Doumazos, Spyridon ^{[1
]}

Aquino, Veronica N. ^{[2
]}

Biasin, Mara ^{[3
]}

Piacentini, Luca ^{[3
]}

Tavano, Barbara ^{[3
]}

Fuchs, Dietmar ^{[4
]}

Mazzotta, Francesco ^{[5
]}

Lo Caputo, Sergio ^{[5
]}

Shearer, Gene M. ^{[6
]}

Clerici, Mario ^{[3
,7
]}

Graham, David R. ^{[2
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Immunol Sect, Chelsea & Westminster Hosp, Div Infect Dis,Dept Med,Fac Med, London SW10 9NH, England

[2] Johns Hopkins Univ, Retrovirus Lab, Dept Mol & Comparat Pathobiol, Sch Med, Baltimore, MD USA

[3] Univ Milan, Cattedra Immunol, Milan, Italy

[4] Innsbruck Med Univ, Div Biol Chem Bioctr, Innsbruck, Austria

[5] Osped SM Annunziata, Div Malattie Infett, Florence, Italy

[6] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[7] Fdn Don C Gnocchi, Ist Ricovero & Cura Carattere Sci, Milan, Italy

来源：

BLOOD | 2011年 / 118卷 / 19期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; APOPTOSIS-INDUCING LIGAND; IMMUNE ACTIVATION; INDOLEAMINE 2,3-DIOXYGENASE; TRYPTOPHAN CATABOLISM; I INTERFERON; LIPID RAFTS; INFECTION; RECEPTOR; INNATE;

D O I：

10.1182/blood-2011-03-344218

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Adelicate balance between immunostimulatory and immunosuppressive signals mediated by dendritic cells (DCs) and other antigen-presenting cells (APCs) regulates the strength and efficacy of antiviral T-cell responses. HIV is a potent activator of plasmacytoid DCs (pDCs), and chronic pDC activation by HIV promotes the pathogenesis of AIDS. Cholesterol is pivotal in maintaining HIV envelope integrity and allowing HIV-cell interaction. By depleting envelope-associated cholesterol to different degrees, we generated virions with reduced ability to activate pDCs. We found that APC activation was dissociated from the induction of type I IFN-alpha/beta and indoleamine-2,3-dioxygenase (IDO)-mediated immunosuppression in vitro. Extensive cholesterol withdrawal, resulting in partial protein and RNA loss from the virions, rendered HIV a more powerful recall immunogen for stimulating memory CD8 T-cell responses in HIV-exposed, uninfected individuals. These enhanced responses were dependent on the inability of cholesterol-depleted HIV to induce IFN alpha/beta. (Blood. 2011;118(19):5152-5162)

引用

页码：5152 / 5162

页数：11

共 45 条

[1]

Triggering TLR7 in mice induces immune activation and lymphoid system disruption, resembling HIV-mediated pathology [J].