CD163/CD16 coexpression by circulating Monocytes/Macrophages in HIV: Potential biomarkers for HIV infection and AIDS progression

Monocytes and macrophages play a prominent role in the establishment of HIV-1 infection, virus dissemination, and development of viral reservoirs. Like T cells, macrophages display immune polarization that can promote or impair adaptive immunity. We hypothesize that dysregulation of monocyte/macrophage activation and differentiation may promote immune dysfunction and contribute to AIDS pathogenesis. Using flow cytometry, we analyzed the frequency of monocyte subsets in human immunodeficiency virus type 1 (HIV-1) infection relative to seronegative controls, focusing on the CD163(+)/CD16(+) monocyte as a likely precursor of the alternatively activated macrophage. Individuals with detectable HIV-1 infection showed an increase in the frequency of CD163(+)/CD16(+) monocytes (CD14(+)) when compared to seronegative or HIV-1-infected persons with undetectable viral loads. A positive correlation between increased CD163(+)/CD16(+) monocyte frequency and viral load was revealed that was not seen between viral load and the number of CD4(+) T cells or frequency of CD16(+) monocytes without CD163 subtyping). We also found a strong inverse correlations between CD16(+) monocytes ( r = -0.71, r(2) = 0.5041, p = 0.0097) or CD163(+)/ CD16+ monocytes ( r = - 0.86, r(2) = 0.7396, p = 0.0003) and number of CD4(+) T cells below 450 cells/mu l. An inverse relationship between CD163(+)/ CD16(+) and CD163 (+)/ CD16(+) monocytes suggests the expanded CD163 (+)/CD16(+) population is derived exclusively from within the alternatively activated ( M Phi-2) subset. These data suggest a potential role for CD163 (+)/ CD16(+) monocytes in virus production and disease progression. CD163(+)/CD16(+) monocytes may be a useful biomarker for HIV1 infection and AIDS progression and a possible target for therapeutic intervention.