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 language | English |
|---|---|
| Pages (from-to) | 5152-5162 |
| Number of pages | 11 |
| Journal | Blood |
| Volume | 118 |
| Issue number | 19 |
| DOIs | |
| Publication status | Published - Nov 10 2011 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Overactivation of plasmacytoid dendritic cells inhibits antiviral T-cell responses
T2 - A model for HIV immunopathogenesis
AU - Boasso, Adriano
AU - Royle, Caroline M.
AU - Doumazos, Spyridon
AU - Aquino, Veronica N.
AU - Biasin, Mara
AU - Piacentini, Luca
AU - Tavano, Barbara
AU - Fuchs, Dietmar
AU - Mazzotta, Francesco
AU - Lo Caputo, Sergio
AU - Shearer, Gene M.
AU - Clerici, Mario
AU - Graham, David R.
PY - 2011/11/10
Y1 - 2011/11/10
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2011-03-344218
DO - 10.1182/blood-2011-03-344218
M3 - Article
VL - 118
SP - 5152
EP - 5162
JO - Blood
JF - Blood
SN - 0006-4971
IS - 19
ER -