Shared monocyte subset phenotypes in HIV-1 infection and in uninfected subjects with acute coronary syndrome

Abstract

The mechanisms responsible for increased cardiovascular risk associated with HIV-1 infection are incompletely defined. Using flow cytometry, in the present study, we examined activation phenotypes of monocyte subpopulations in patients with HIV-1 infection or acute coronary syndrome to find common cellular profiles. Nonclassic (CD14+CD16++) and intermediate (CD14++CD16+) monocytes are proportionally increased and express high levels of tissue factor and CD62P in HIV-1 infection. These proportions are related to viremia, T-cell activation, and plasma levels of IL-6. In vitro exposure of whole blood samples from uninfected control donors to lipopolysaccharide increased surface tissue factor expression on all monocyte subsets, but exposure to HIV-1 resulted in activation only of nonclassic monocytes. Remarkably, the profile of monocyte activation in uncontrolled HIV-1 disease mirrors that of acute coronary syndrome in uninfected persons. Therefore, drivers of immune activation and inflammation in HIV-1 disease may alter monocyte subpopulations and activation phenotype, contributing to a pro-atherothrombotic state that may drive cardiovascular risk in HIV-1 infection.

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

“…This was the first report of the monocyte subset distribution in primary HIV-1 infection, and it expanded previous observations that had focused on chronic HIV-1-infected patients, HARRT patients, and elite controllers. 16,17,30 In contrast to the report by Han et al, 16 we found that CD14 dim CD16 1 and CD14 high CD16 2 monocytes were negatively correlated with CD4 counts in PHI but not CHI. This difference might be due to our limited case numbers in the CHI group.…”

“…[22][23][24] Increased immune activation of monocytes was reported to be involved in HIV-1 pathogenesis and thus associated with CVD risk. 17,28,29 In the present study, we demonstrated that in contrast to the decreased percentage of CD14 high CD16 2 monocyte subset, CD14 dim CD16 1 and CD14 high CD16 1 monocyte subsets were expanded during both primary and chronic HIV-1 infection. This was the first report of the monocyte subset distribution in primary HIV-1 infection, and it expanded previous observations that had focused on chronic HIV-1-infected patients, HARRT patients, and elite controllers.…”

“…14,15 Increased proportions of non-classical and intermediate monocytes have been indicated in HIV-1 infected patients. 16,17 However, the phenotypic characteristics of specific monocyte subsets and their association with immune activation markers have not been fully defined. Recently, monocyte subset alterations and the formation of monocyte-platelet aggregates (MPAs) have been reported to be highly correlated with cardiovascular events.…”

IFN-Stimulated Gene LY6E in Monocytes Regulates the CD14/TLR4 Pathway but Inadequately Restrains the Hyperactivation of Monocytes during Chronic HIV-1 Infection

“…7A, 7B), indicating that monocytes from HIV patients are in a heightened activation state perhaps owing to persistent viral replication, exposure to homeostatic cytokines, and to microbial products (33)(34)(35). Furthermore, to directly examine the immunosuppressive role of LY6E in HIV infection, CD14…”

The hidden risk: Incorporating inflammation and HIV serostatus into coronary artery disease screening

“…Of these comorbidities, the management of CAD has been a point of emphasis. Infection with HIV leads to dysregulation of the immune system resulting in immune hyperactivation 5,6 and a systemic ''cytokine storm.'' 7 Furthermore, coronary atherosclerotic lesions in HIV-infected patients are often unstable and more prone to rupture, resulting in a 1.5-twofold higher incidence of acute coronary syndrome and myocardial infarction.…”