Plasmacytoid dendritic cells (pDC) provide an important link between innate and acquired immunity, mediating their action\nmainly through IFN-a production. pDC suppress HIV-1 replication, but there is increasing evidence suggesting they may also\ncontribute to the increased levels of cell apoptosis and pan-immune activation associated with disease progression. Although\nhaving the same clinical spectrum, HIV-2 infection is characterized by a strikingly lower viremia and a much slower rate of CD4\ndecline and AIDS progression than HIV-1, irrespective of disease stage. We report here a similar marked reduction in circulating\npDC levels in untreated HIV-1 and HIV-2 infections in association with CD4 depletion and T cell activation, in spite of the\nundetectable viremia found in the majority of HIV-2 patients. Moreover, the same overexpression of CD86 and PD-L1 on\ncirculating pDC was found in both infections irrespective of disease stage or viremia status. Our observation that pDC\ndepletion occurs in HIV-2 infected patients with undetectable viremia indicates that mechanisms other than direct viral\ninfection determine the pDC depletion during persistent infections. However, viremia was associated with an impairment of\nIFN-a production on a per pDC basis upon TLR9 stimulation. These data support the possibility that diminished function in\nvitro may relate to prior activation by HIV virions in vivo, in agreement with our finding of higher expression levels of the IFN-a\ninducible gene, MxA, in HIV-1 than in HIV-2 individuals. Importantly, serum IFN-a levels were not elevated in HIV-2 infected\nindividuals. In conclusion, our data in this unique natural model of ââ?¬Ë?ââ?¬Ë?attenuatedââ?¬â?¢Ã¢â?¬â?¢ HIV immunodeficiency contribute to the\nunderstanding of pDC biology in HIV/AIDS pathogenesis, showing that in the absence of detectable viremia a major depletion\nof circulating pDC in association with a relatively preserved IFN-a production does occur.
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