Overactivation of Plasmacytoid Dendritic Cells Inhibits Antiviral T-cell Responses: a Model for HIV Immunopathogenesis

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2011 Sep 21

PMID 21931112

Citations 28

Authors

Adriano Boasso

Caroline M Royle

Spyridon Doumazos

Veronica N Aquino

Mara Biasin

Luca Piacentini

Barbara Tavano

Dietmar Fuchs

Francesco Mazzotta

Sergio Lo Caputo

Gene M Shearer

Mario Clerici

David R Graham

Affiliations

Soon will be listed here.

Abstract

A delicate 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-α/β 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-α/β.

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