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.

Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses : a model for HIV immunopathogenesis / A. Boasso, C.M. Royle, S. Doumazos, V.N. Aquino, M. Biasin, L. Piacentini, B. Tavano, D. Fuchs, F. Mazzotta, S. Lo Caputo, G.M. Shearer, M. Clerici, D. R. Graham .. - In: BLOOD. - ISSN 0006-4971. - 118:19(2011), pp. 5152-5162. [10.1182/blood-2011-03-344218]

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

M. Biasin;B. Tavano;M. Clerici;
2011

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.
Settore MED/04 - Patologia Generale
Settore BIO/13 - Biologia Applicata
BLOOD
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/178399
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