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

• Published in: PloS one 2010-03, Vol.5 (3), p.e9643
• Main Authors: Leeansyah, Edwin, Zhou, Jingling, Paukovics, Geza, Lewin, Sharon R., Crowe, Suzanne M., Jaworowski, Anthony
• Format: Article
• Language: English
• Subjects: Antigens; Antiretroviral agents; Antiretroviral drugs; Antiretroviral therapy; Blood; CD56 antigen; Cell activation; Cross-sectional studies; Drug therapy; Ethics; Gene expression; HIV; Human immunodeficiency virus; Immune system; Immunoblotting; Immunoglobulins; Immunology/Innate Immunity; Immunology/Leukocyte Signaling and Gene Expression; Immunoreceptor tyrosine-based activation motif; Infections; Infectious diseases; Infectious Diseases/HIV Infection and AIDS; Inflammatory diseases; Leukocytes (mononuclear); Lymphocytes; Macrophages; Medical research; Medicine; Monocytes; mRNA; Natural killer cells; Patients; Peripheral blood mononuclear cells; Proteins; Public health; Receiving; Signaling; T cell receptors; Therapy; Tyrosine; Virology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0009643

Background FcRγ 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 FcRγ is down-regulated in HIV-infected macrophages in vitro. FcRγ expression in immune cells present in HIV-infected individuals is unknown. Methodology/Principal Findings We compared FcRγ expression in peripheral blood mononuclear cells isolated from HIV-1-infected individuals receiving combination antiretroviral therapy and healthy, HIV-1-uninfected individuals. FcRγ 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 FcRγ 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 FcRγ protein expression compared to uninfected controls (decrease = 50.2%, n = 9 and n = 8 respectively, p = 0.021). Decreased FcRγ 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.