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.Cellular & Molecular Immunology advance online publication, 11 August 2014; doi:10.1038/cmi.2014.66.

Figure 1

Altered distributions of monocyte subsets in HIV-1 infection. (a) Gating strategies of monocyte subsets according to CD14 and CD16 expression. (b) Frequencies (%) of CD14^dimCD16⁺, CD14^highCD16+ and CD14^highCD16⁻ monocyte subsets in primary HIV-1 infection (PHI, n=38), chronic HIV-1 infection (CHI, n=20), and healthy controls (HC, n=26). The lines show the median with the interquartile range. (c) Correlation analyses for CD14^dimCD16⁺, CD14^highCD16⁺ and CD14^highCD16⁻ monocyte subsets vs. CD4 T-cell counts in PHI (n=38). P<0.05 indicates significance.

Figure 2

Increased MPA formation in CD14^dimCD16⁺, CD14^highCD16⁺ and CD14^highCD16⁻ monocyte subsets during HIV-1 infection. (a) MPA levels, as represented by the percentage of CD61⁺ cells, in individual monocyte subsets in PHI, CHI and healthy controls. The lines show the median with the interquartile range. (b) Correlation analyses for MPA levels in each monocyte subsets vs. the plasma viral load in HIV-1 infection (n=58). (c) PSGL-1 expression on three monocyte subsets in PHI, CHI and healthy controls. The data are shown as the MFI, and the lines show the median with the interquartile range. (d) Correlation analyses for MPA levels vs. PSGL-1 expression intensity in each monocyte subset in HIV-1 infection (n=58). P<0.05 indicates significance. CHI, chronic HIV-1 infection; MFI, mean fluorescent intensity; MPA, monocyte–platelet aggregate; PHI, primary HIV-1 infection; PSGL-1, P-selectin glycoprotein ligand-1.

Figure 3

Increased expression of surface immune activation markers on monocyte subsets in HIV-1 infection. Expression of TLR2 (a), TLR4 (b), PD-L1 (c) and PD-1 (d) on CD14^dimCD16⁺, CD14^highCD16⁺ and CD14^highCD16⁻ monocyte subsets in PHI, CHI and healthy controls. The data are shown as the MFI. The lines show the median with the interquartile range. P<0.05 indicates significance. CHI, chronic HIV-1 infection; MFI, mean fluorescent intensity; PD-1, programmed death 1; PHI, primary HIV-1 infection; TLR, Toll-like receptor.

Figure 4

Plasma levels of sCD14 and sCD163 in HIV-1 infection were altered and were positively correlated with HIV-1 viremia and negatively correlated with CD4 T-cell counts. (a) Plasma samples were tested for sCD14 and sCD163 levels by ELISA. The lines show the median with the interquartile range. (b) Correlation analyses of increased levels of sCD14 and sCD163 in the plasma vs. the CD4 T-cell counts (left panel) or vs. the plasma viral load (right panel) (n=58). P<0.05 indicates significance. CHI, chronic HIV-1 infection; HC, healthy control; PHI, primary HIV-1 infection.

Figure 5

Plasma levels of sCD163 were correlated with MPA levels and inversely correlated with PSGL-1 and CD163 expression in all three monocyte subsets. (a) Correlation analyses of PSGL-1 expression on CD14^dimCD16⁺, CD14^highCD16⁺ and CD14^highCD16⁻ monocyte subsets vs. sCD163 level in plasma (n=58). (b) Correlation analyses of MPA levels on CD14^dimCD16⁺, CD14^highCD16⁺ and CD14^highCD16⁻ monocyte subsets vs. sCD163 levels in the plasma (upper panel) or vs. CD163 expression on monocyte subsets (lower panel) (n=58). P<0.05 indicates significance. MPA, monocyte–platelet aggregate; PSGL-1, P-selectin glycoprotein ligand-1.