Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy

作者：You-Yuan Wang, Cheng Zhen, Wei Hu, Hui-Huang Huang, Yanjun Li, Ming‐Ju Zhou, Jing Li, Yulong Fu, Peng Zhang, Xiaoyu Li, Tao Yang, Jin‐Wen Song, Xing Fan, Jun Zou, Si-Run Meng, Yaqin Qin, Yan‐Mei Jiao, Ruonan Xu, Ji‐Yuan Zhang, Chun‐Bao Zhou, Jin‐Hong Yuan, Lei Huang, Ming Shi, Liang Cheng, Fu‐Sheng Wang, Chao Zhang · 发表于：Communications Biology · 年份：2023 · DOI：10.1038/s42003-023-04975-z · 被引用次数：11 · 研究领域：HIV Research and Treatment、Immune Cell Function and Interaction、T-cell and B-cell Immunology

CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.