Higher levels of circulating monocyte–platelet aggregates are correlated with viremia and increased sCD163 levels in HIV-1 infection

Abstract

Increased levels of monocyte-platelet aggregates (MPAs) are reported to be highly correlated with cardiovascular events. In this study, the MPA levels in different monocyte subsets and the associations between MPA levels, HIV-1 viremia and monocyte activation were evaluated during HIV-1 infection. The results showed that the percentages of MPAs in all three monocyte subsets were higher in HIV-1-infected subjects than in healthy controls, and were associated with the plasma viral load in the non-classical and intermediate monocyte subsets. The plasma levels of sCD14 and sCD163 were upregulated in HIV-1 infection and were positively associated with viral loads and negatively associated with CD4 counts. P-selectin glycoprotein ligand-1 (PSGL-1) was shown to be expressed at significantly lower levels on all three monocyte subsets and was negatively correlated with the sCD163 level. The MPA level was correlated with the levels of plasma sCD163 but negatively correlated with CD163 and PSGL-1 on all three monocyte subsets. An elevated immune activation status was correlated with increased MPA formation, underlying the potential interaction between monocyte activation and MPA formation. This interaction may be related to a higher thromboembolic risk in patients infected with HIV-1.

Immune activation and cardiovascular disease in chronic HIV infection

“…Additional HIV associated monocyte abnormalities, related to impaired cholesterol efflux by foam cells and pro-coagulant effects (e.g., related to platelet-monocyte complexes), then further contribute to CVD risk. [63-65] For example, monocytes from HIV+ subjects are more likely to become foam cells, have decreased expression of the cholesterol transporter ABCA1, and show impaired cholesterol efflux[66]. Dysfunctional HDL appears to further impair reverse cholesterol transport from macrophages, but this improves with ART[64].…”

Role of immune activation in progression to AIDS

“…HIV results in a shift from “classical” CD14++CD16− to “non-classical” CD14+CD16+ and “intermediate” CD14++CD16+ monocytes, which are associated with an inflammatory phenotype [40–42] and greater viremia and/or CD4+ T cell depletion [42, 43]. High expression of the PD1 homologue (PD-1H), which is associated with increased production of TNF, IL-1β, and IL-6, may also contribute to the pro-inflammatory state of these monocytes [44].…”

“…High plasma IP-10, IL-6 and sCD14 all consistently predict increased subsequent morbidity and mortality during ART [42, 43, 60], and high sCD163 levels have been associated with surrogate markers of neurologic and cardiovascular disease (though perhaps not cardiovascular events [61]), as well as all-cause mortality in a recent report [26, 57–59, 62, 63]. As many of these biomarkers of monocyte activation may be increased by smoking and/or alcohol use, many of these associations with morbidity and mortality may be at least in part driven by behavioral risk factors and not HIV itself, though a recent report suggests that these associations persist despite adjustment for behavioral risk factors [64].…”

Statin modulation of monocyte phenotype and function: implications for HIV-1-associated neurocognitive disorders

“…Numerous CD163+ cells in HIVE and SIV encephalitis (SIVE) further suggest entry of monocytes into the CNS from the peripheral blood (Kim, Alvarez et al 2006), since CD163 is not expressed by resident brain microglia and increased CD163+CD16+ monocytes in the periphery is associated with increased frequency of CD163+CD16+ M/M in the CNS (Clay, Rodrigues et al 2007; Fischer-Smith, Bell et al 2008). Elevated sCD163 in plasma, a result of surface CD163 shedding in response to pro-inflammatory stimuli, is also associated with neurocognitive impairment in HIV-1 infection (Moller 2012; Burdo, Weiffenbach et al 2013; Liang, Duan et al 2014; Wilson, Singh et al 2014). These findings highlight the importance of CD16+ monocytes as a link between peripheral immune activation and CNS disease, as well as CD163+ cells.…”