Department of Microbiology and Immunology, Institute for Molecular Medicine & Infectious Disease, Drexel University College of Medicine, Philadelphia, Pennsylvania, United States of America.
Centre for Innovation Competence (ZIK) plasmatis, Leibniz Institute for Plasma Science and Technology Greifswald (INP), Greifswald, Germany.
PLoS One. 2021 Mar 1;16(3):e0247125. doi: 10.1371/journal.pone.0247125. eCollection 2021.
Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH.
有效控制人类免疫缺陷病毒 1 型（HIV-1）感染，HIV-1 是获得性免疫缺陷综合征（AIDS）的病原体，需要 HIV-1 感染者（PLWH）持续和终身使用抗逆转录病毒治疗（ART）。如果先天和细胞毒性 T 淋巴细胞反应不佳，潜伏感染的细胞中的 HIV-1 重新出现将无法有效抑制。然而，如果可以逆转或恢复固有免疫缺陷，可能可以实现无需 ART 即可控制 HIV-1 感染。在此，我们提出了一种调节 HIV-1 免疫反应的新方法，该方法涉及使用非热等离子体（NTP），它是一种包含各种活性氧和氮物种（RONS）的电离气体。J-Lat 细胞被用作潜伏 HIV-1 感染的模型，以评估 NTP 应用对病毒潜伏和吞噬和趋化损伤相关分子模式（DAMPs）表达的影响。NTP 暴露于 J-Lat 细胞导致 HIV-1 基因表达的刺激，表明在诱导针对病毒抗原的适应性免疫反应中起着逆转潜伏的作用，这是一个必要的第一步。这伴随着促炎细胞因子和趋化因子（包括白细胞介素-1β（IL-1β）和干扰素-γ（IFN-γ））的释放；吞噬标记物钙网蛋白（CRT），热休克蛋白（HSP）70 和 90 的表达；以及巨噬细胞对 NTP 暴露的 J-Lat 细胞的吞噬作用相关增加。此外，还观察到促进或抑制抗原呈递的表面分子的调制，以及 MHC I 上显示的肽的改变排列，这进一步表明 NTP 可能修饰潜伏 HIV-1 感染中细胞的识别和靶向的方法。这些研究代表了基于 NTP 的有效体外免疫疗法的早期进展，以解决使 HIV-1 在 PLWH 中持续存在的免疫系统功能障碍。
