Tomescu Costin, Colon Krystal, Smith Peter, Taylor Mack, Azzoni Livio, Metzger David S, Montaner Luis J
HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, Pennsylvania, USA.
Department of Psychiatry, HIV Prevention Division, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Leukoc Biol. 2020 Dec 2. doi: 10.1002/JLB.5A0920-604R.
Previous literature suggests that acute opioid use results in the functional impairment of the immune response, thereby decreasing resistance to viral infection. Here, we assessed if innate and adaptive immune responses are compromised ex vivo in persons who inject drugs (PWID) and whether long-term injection drug use may impact host susceptibility to in vitro HIV infection. We measured the frequency, activation state, and functional profile of NK cells, dendritic cells, and CD4 and CD8 T cells in low-risk PWID who do not share needles, high-risk needle-sharing PWID, and control donors who did not inject drugs. We also assessed plasma levels of inflammatory markers and CD4 T cell susceptibility to HIV infection. We observed a significant increase in the amount of sCD14 (P = 0.0023, n = 16) and sCD163 (P = 0.0001, n = 16) in the plasma of PWID compared to controls. Evidence of constitutive activation was noted in PWID as compared to controls with increased CD69 expression in CD56 NK cells (P = 0.0103, n = 26) and increased CD38 and HLA-DR expression in CD4 T cells (P = 0.0355, n = 23). However, no innate or adaptive functional differences were detected between PWID and controls, including: NK cell direct or antibody-dependent cellular cytotoxicity poly-functional response, TLR-stimulated dendritic cell/NK crosstalk, CD8 T cell response to Staphylococcal enterotoxin B or CMV/EBV/FLU peptides, or constitutive or anti-CD3/CD28-stimulated CD4 T cell infectivity with CCR5-tropic or CXCR4-tropic HIV-1 isolates. Our data indicate that PWID who utilize opioids over as prolonged time frame can retain a functional ex vivo immune response without a measurable increase in CD4 T cell infectivity suggesting that leukocytes from PWID are not intrinsically more susceptibility to infection with HIV than non-PWID controls.
以往文献表明，急性使用阿片类药物会导致免疫反应功能受损，从而降低对病毒感染的抵抗力。在此，我们评估了注射吸毒者（PWID）的先天性和适应性免疫反应在体外是否受到损害，以及长期注射吸毒是否会影响宿主对体外HIV感染的易感性。我们测量了不共用针头的低风险PWID、高风险共用针头的PWID以及不注射毒品的对照供者中自然杀伤细胞、树突状细胞、CD4和CD8 T细胞的频率、激活状态和功能特征。我们还评估了炎症标志物的血浆水平以及CD4 T细胞对HIV感染的易感性。与对照组相比，我们观察到PWID血浆中可溶性CD14（P = 0.0023，n = 16）和可溶性CD163（P = 0.0001，n = 16）的量显著增加。与对照组相比，在PWID中观察到组成性激活的证据，CD56自然杀伤细胞中CD69表达增加（P = 0.0103，n = 26），CD4 T细胞中CD38和HLA - DR表达增加（P = 0.0355，n = 23）。然而，在PWID和对照组之间未检测到先天性或适应性功能差异，包括：自然杀伤细胞直接或抗体依赖性细胞毒性多功能反应、Toll样受体刺激的树突状细胞/自然杀伤细胞串扰、CD8 T细胞对葡萄球菌肠毒素B或巨细胞病毒/EB病毒/流感肽的反应，或组成性或抗CD3/CD28刺激的CD4 T细胞对CCR5嗜性或CXCR4嗜性HIV - 1分离株的感染性。我们的数据表明，长期使用阿片类药物的PWID可以在体外保留功能性免疫反应，而CD4 T细胞感染性没有可测量的增加，这表明来自PWID的白细胞在感染HIV方面并不比非PWID对照者更具内在易感性。
