Decreased NK Cell FcRγ in HIV-1 Infected Individuals Receiving Combination Antiretroviral Therapy: a Cross Sectional Study

Background: FcR gamma is an immunoreceptor tyrosine-based activation motif (ITAM)-signalling protein essential for immunoreceptor signaling and monocyte, macrophage and NK cell function. Previous study from our laboratory showed that FcR gamma is down-regulated in HIV-infected macrophages in vitro. FcR gamma expression in immune cells present in HIV-infected individuals is unknown. Methodology/Principal Findings: We compared FcR gamma expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcR gamma mRNA and protein levels were measured using quantitative real-time PCR and immunoblotting, respectively. CD56(+) CD94(+) lymphocytes isolated from blood of HIV-1 infected individuals had reduced FcR gamma protein expression compared to HIV-uninfected individuals (decrease = 76.8%, n = 18 and n = 12 respectively, p = 0.0036). In a second group of patients, highly purified NK cells had reduced FcR gamma protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021). Decreased FcR gamma expression in CD56(+) CD94(+) lymphocytes was associated with reduced mRNA (51.7%, p = 0.021) but this was not observed for the smaller group of patients analysed for NK cell expression (p = 0.36). Conclusion/Significance: These data suggest biochemical defects in ITAM-dependent signalling within NK cells in HIV-infected individuals which is present in the context of treatment with combination antiretroviral therapy.