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.
|Titolo:||Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses : a model for HIV immunopathogenesis.|
CLERICI, MARIO SALVATORE (Penultimo)
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1182/blood-2011-03-344218|
|Appare nelle tipologie:||01 - Articolo su periodico|