Phenotypic characterisation of activated plasmacytoid dendritic cells among anti-retroviral therapy-naïve Ugandans with chronic HIV-1 clade A or D infection.
Senkandwa, Kyabaggu Denis
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Plasmacytoid dendritic cells (pDC) are the most potent producers of interferon alpha (IFN-α) and tumor necrosis factor alpha (TNF-α) in response to enveloped viruses providing a critical link between the innate and adaptive immune responses. The loss of peripheral blood pDC function and numbers has been linked to HIV-1 disease progression. Studies have demonstrated that both acute and chronic HIV-1 infections resulted in the alteration of pDC frequency, phenotype, functional impairment of IFN-α-release and T-cell activity in both adult and pediatric individuals. 50 samples of chronically HIV-1 infected Ugandans and 10 HIV-1 negative samples were analyzed for the phenotype and function of pDCs by flow cytometry. Five HIV-1 negative PBMC samples from Thai donors were also analysed. pDCs were stained for surface, co-stimulatory and activation markers, followed by intracellular cytokine staining to measure the expression of IFN-α and TNF- α after stimulation with different antigens over night. The frequency of pDCs in HIV-1 infected Ugandans was reduced compared to uninfected individuals. There was a significant inverse correlation between pDC percentages and the absolute CD4+ T cell count. A significant down regulation of CD80 in HIV-1 subtype D infected subjects when compared to HIV-1 subtype A infected subjects was also observed. A strong increase in IFN-α production was seen in HIV-1 positive cells after stimulation with TLR7/8 agonist but not observed after stimulation with either whole inactivated virus HIV-1 subtype A or D. After stimulation with influenza A virus, the expression of IFN-α, but not TNF-α, increased in both HIV-1 positive and in HIV-1 negative subjects. Overall, the phenotype of pDC’s remains relatively unchanged in chronic HIV-1 A or D infection, although the surface expression of CD80 appears down regulated during chronic HIV-1 subtype D infection relative to HIV-1 subtype A. The ability of pDCs to produce IFN-α and TNF-α after certain in vitro stimulation seems to be inhibited in chronic HIV-1 A or D infections.