CD163/CD16 coexpression by circulating monocytes/macrophages in HIV: potential biomarkers for HIV infection and AIDS progression

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, 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/microl. An inverse relationship between CD163(+)/CD16(+) and CD163(+)/CD16() monocytes suggests the expanded CD163(+)/CD16(+) population is derived exclusively from within the "alternatively activated" (MPhi-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.

Figure 1. The frequency of CD163⁺/CD16⁺ monocytes is greater in patients with detectable viral loads

The frequency of CD163⁺/CD16⁺ monocytes (CD14⁺) is significantly increased in HIV-1 infected individuals with detectable plasma viremia when compared to seronegative donors or patients with HIV-1 infection who are successfully controlling virus with pharmaceutical intervention. A slight reduction in the number of CD163⁺/CD16⁺ monocytes is seen with virus suppression as compared to seronegative individuals, however this is not statistically significant. All “undetectable” HIV-1 infected subjects were on ARV. Only a single donor within the “detectable” group was on ARV.

Figure 2. CD163⁺/CD16⁺ monocyte expansion correlates positively with viral load and inversely with CD4⁺ T cell number in HIV-1 infected individuals

Pearson correlation statistics demonstrate a significant correlation between expansion of the CD163⁺/CD16⁺ monocyte subset with increasing viral burden (Panel A). Further, in HIV-1 infected individuals with CD4⁺ T cell counts below 450 cells/μl (12 of 19 subjects), an inverse correlation was seen between absolute number of CD4⁺ T cells and CD16⁺ or CD163⁺/CD16⁺ monocyte frequency, with greater significance seen with CD163⁺/CD16⁺ monocyte (r² = 74%) (Panels B and C) than CD16⁺ monocyte frequency (r² = 50%) (Panel C). Data analyses were performed using the original viral load values. Viral loads were log transformed after analyses for data presentation.