CD163/CD16 Coexpression by Circulating Monocytes/Macrophages in HIV: Potential Biomarkers for HIV Infection and AIDS Progression

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Abstract
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, r2 = 0.5041, p = 0.0097) or CD163+/CD16+ monocytes (r = −0.86, r2 = 0.7396, p = 0.0003) and number of CD4+ T cells below 450 cells/μl. An inverse relationship between CD163+/CD16+ and CD163+/CD16− monocytes suggests the expanded CD163+/CD16+ population is derived exclusively from within the “alternatively activated” (MΦ-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 HIV-1 infection and AIDS progression and a possible target for therapeutic intervention.