Unknown

Dataset Information

0

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


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-?/? 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-?/?.

SUBMITTER: Boasso A 

PROVIDER: S-EPMC3217402 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 degre  ...[more]

Similar Datasets

| S-EPMC4117636 | biostudies-literature
| S-EPMC6013066 | biostudies-literature
| S-EPMC4820019 | biostudies-literature
| S-EPMC1866176 | biostudies-literature
| S-EPMC1805537 | biostudies-literature
| S-EPMC4761472 | biostudies-literature
| S-EPMC3318617 | biostudies-literature
| S-EPMC3504132 | biostudies-other
| S-EPMC8221820 | biostudies-literature
| S-EPMC3098498 | biostudies-literature