Upregulation of IFN-γ-induced STAT1 activation and apoptosis in monocytes from HIV plus patients

Monocytes/macrophages are critical for pathogen clearance. We have shown that in contrast to IFN-alpha, IFN-gamma-induced tyr-phosphorylated STAT1 (P-STAT1) was significantly upregulated in monocytes from HIV+ patients off therapy compared to HIV- controls and HIV+ patients on antiretroviral therapy (ART). P-STAT1 upregulation appeared to be due to increased total STAT1 protein expression. As a follow up to this observation, we found that spontaneous and IFN-gamma-induced monocyte apoptosis was elevated in HIV+ patients compared to HIV- controls. Spontaneous apoptosis correlated with plasma TRAIL levels. Amplification of IFN-gamma-induced STATI activation and apoptosis in HIV+ patient monocytes are novel findings that may explain, at least in part, the functional impairment observed in these cells through the course of the disease.