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

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

Research output: Contribution to journalArticle

Abstract

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-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.

Original languageEnglish (US)
Pages (from-to)5152-5162
Number of pages11
JournalBlood
Volume118
Issue number19
DOIs
StatePublished - Nov 10 2011

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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