Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
HIV Vaccine Trials Network, Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Centre, Seattle, USA.
AIDS. 2023 Jun 1;37(7):1023-1033. doi: 10.1097/QAD.0000000000003512. Epub 2023 Mar 21.
Why people with HIV-1 on ART (PWH ART ) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PWH ART and HIV-1 negative individuals (HC).
Cross-sectional study.
Untargeted and targeted metabolomics was performed using gas and liquid chromatography/mass spectrometry, and targeted proteomics using Olink inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes.
We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g. CCL20 and CCL7) in PWH ART compared to HC. The metabolite transporter detection by flow cytometry in T cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PWH ART . Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PWH ART . Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells.
Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 infection.
为什么接受抗逆转录病毒疗法（ART）的 HIV-1 感染者（PWHART）在长期抑制性治疗期间表现出复杂的代谢和免疫细胞功能，目前尚未得到很好的评估。在这项研究中，我们旨在使用多组学方法来解决这个问题，以研究 PWHART 与 HIV-1 阴性个体（HC）之间的免疫和代谢差异。
横断面研究。
使用气相和液相色谱/质谱联用技术进行非靶向和靶向代谢组学分析，使用 Olink 炎症面板进行靶向蛋白质组学分析，对血浆样本进行分析。使用流式细胞术进一步研究细胞的代谢状态，并使用 EasySep 细胞分离技术分离的单细胞群进行细胞内代谢测量。最后，通过流式细胞术对单核吞噬细胞进行深度免疫表型分析。
我们通过血浆代谢组学检测到 PWHART 中谷氨酸、乳酸和丙酮酸水平升高，并且与 HC 相比，PWHART 中炎症标志物（如 CCL20 和 CCL7）水平升高。T 细胞和单核细胞中代谢物转运体的流式细胞术检测表明，PWHART 中葡萄糖转运蛋白 1（Glut1）和单羧酸转运蛋白 1（MCT-1）的表达增加。单细胞类型代谢物测量确定了 PWHART 中单核细胞群体中葡萄糖、谷氨酸和乳酸水平降低。髓样细胞谱系亚群的深度免疫表型分析显示，细胞频率无差异，但经典单核细胞和一些树突状细胞上的 CCR5 表达水平增加。
因此，我们的数据表明，髓样细胞群可能在抑制性 HIV-1 感染期间对调节代谢环境做出重要贡献。
