Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

Article

关键词: IMMUNODEFICIENCY-VIRUS TYPE-1;    EX-VIVO;    DENDRITIC CELLS;    LYMPHOID-TISSUE;    APOPTOSIS;    ACTIVATION;    INHIBITORS;    MATURATION;    IL-1-BETA;    MONOCYTES;   

DOI  :  10.1038/nature12940

来源: SCIE

【 摘 要 】

The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1 beta, are released. This death pathway thus links the two signature events in HIV infection-CD4 T-cell depletion and chronic inflammation-and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of 'anti-AIDS' therapeutics targeting the host rather than the virus.

【 授权许可】

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