*Department of Medicine, Division of Infectious Diseases, University of Colorado Denver, Aurora, CO; and †Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL.
J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):259-67. doi: 10.1097/01.qai.0000435603.50598.2b.
Natural killer (NK) cells are important in innate immune responses to bacterial and viral pathogens. HIV-1 infection is associated with opportunistic bacterial infections and with microbial translocation, but the nature of the NK cell response to bacteria during HIV-1 infection has not been studied extensively. The objective of this study was to compare NK cell responses to bacteria in HIV-1-infected versus that in uninfected individuals.
Multicolor flow cytometry was used to evaluate the ability of blood NK cell subsets (CD56CD16, CD56CD16, and CD56CD16) from treated, virally suppressed, and untreated viremic subjects with chronic HIV-1 infection and uninfected controls, to secrete interferon gamma (IFN-γ) in response to the in vitro stimulation of peripheral blood mononuclear cells with heat-killed commensal Escherichia coli or pathogenic Salmonella typhimurium.
All 3 NK cell subsets produced IFN-γ in response to bacteria, but CD56CD16 NK cells were least responsive. Untreated HIV-1-infected donors had increased frequencies of CD56CD16 NK cells and lower overall frequencies of IFN-γ-producing NK cells responding to E. coli and S. typhimurium than did NK cells from uninfected donors. These NK cell defects were not fully restored in antiretroviral therapy-treated donors. Monocytes were necessary for NK cells to respond to bacteria, but the HIV-associated defect was intrinsic to NK cells because the addition of normal monocytes did not restore IFN-γ production in response to bacteria.
Functional defects and numeric alterations of NK cell subsets lead to decreased frequencies of bacteria-reactive, IFN-γ-producing NK cells in HIV-1-infected subjects, even those on antiretroviral therapy.
自然杀伤 (NK) 细胞在对抗细菌和病毒病原体的先天免疫反应中具有重要作用。HIV-1 感染与机会性细菌感染和微生物易位有关，但 HIV-1 感染期间 NK 细胞对细菌的反应性质尚未得到广泛研究。本研究的目的是比较 HIV-1 感染与未感染个体对细菌的 NK 细胞反应。
使用多色流式细胞术评估来自接受治疗、病毒抑制和未治疗的病毒血症慢性 HIV-1 感染患者以及未感染对照者的血液 NK 细胞亚群（CD56CD16、CD56CD16 和 CD56CD16）在体外刺激外周血单个核细胞时分泌干扰素 γ (IFN-γ) 的能力与热灭活共生大肠杆菌或致病性鼠伤寒沙门氏菌。
所有 3 种 NK 细胞亚群均对细菌产生 IFN-γ，但 CD56CD16 NK 细胞反应性最低。未经治疗的 HIV-1 感染供体中 CD56CD16 NK 细胞的频率增加，对大肠杆菌和鼠伤寒沙门氏菌的 IFN-γ 产生 NK 细胞的总频率降低，而未感染供体的 NK 细胞频率降低。这些 NK 细胞缺陷在抗逆转录病毒治疗的供体中并未完全恢复。单核细胞对于 NK 细胞对细菌的反应是必需的，但 HIV 相关缺陷是 NK 细胞固有的，因为添加正常单核细胞并不能恢复对细菌的 IFN-γ 产生。
NK 细胞亚群的功能缺陷和数量改变导致 HIV-1 感染受试者中对细菌有反应、产生 IFN-γ 的 NK 细胞频率降低，即使是接受抗逆转录病毒治疗的患者也是如此。
