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

32 Citations (Scopus)

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
Pages (from-to)5152-5162
Number of pages11
JournalBlood
Volume118
Issue number19
DOIs
Publication statusPublished - Nov 10 2011

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T-cells
Dendritic Cells
Antiviral Agents
Cholesterol
HIV
T-Lymphocytes
Chemical activation
Indoleamine-Pyrrole 2,3,-Dioxygenase
Antigen-Presenting Cells
Virion
Immunosuppressive Agents
RNA
Data storage equipment
Cell Communication
Immunosuppression
Acquired Immunodeficiency Syndrome
Proteins

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Boasso, A., Royle, C. M., Doumazos, S., Aquino, V. N., Biasin, M., Piacentini, L., ... 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

Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses : A model for HIV immunopathogenesis. / Boasso, Adriano; Royle, Caroline M.; Doumazos, Spyridon; Aquino, Veronica N.; Biasin, Mara; Piacentini, Luca; Tavano, Barbara; Fuchs, Dietmar; Mazzotta, Francesco; Lo Caputo, Sergio; Shearer, Gene M.; Clerici, Mario; Graham, David R.

In: Blood, Vol. 118, No. 19, 10.11.2011, p. 5152-5162.

Research output: Contribution to journalArticle

Boasso, A, Royle, CM, Doumazos, S, Aquino, VN, Biasin, M, Piacentini, L, Tavano, B, Fuchs, D, Mazzotta, F, Lo Caputo, S, Shearer, GM, Clerici, M & Graham, DR 2011, 'Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses: A model for HIV immunopathogenesis', Blood, vol. 118, no. 19, pp. 5152-5162. https://doi.org/10.1182/blood-2011-03-344218
Boasso, Adriano ; Royle, Caroline M. ; Doumazos, Spyridon ; Aquino, Veronica N. ; Biasin, Mara ; Piacentini, Luca ; Tavano, Barbara ; Fuchs, Dietmar ; Mazzotta, Francesco ; Lo Caputo, Sergio ; Shearer, Gene M. ; Clerici, Mario ; Graham, David R. / Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses : A model for HIV immunopathogenesis. In: Blood. 2011 ; Vol. 118, No. 19. pp. 5152-5162.
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