Mo Lengshan, Hong Cansheng, Jiang Zhihan, Zhu Yiqiang, Zhou Lu, Tan Simin, Deng Guorong, Qi Yanwei, Hu Tengfei, Wu Qianlian, Zhao Yi, Qiu Huaina, Liang Taizhen, Lin Peibin, Zhang Jian, Ma Xiancai, Yang Quan
Department of Pathogenic Biology and Immunology, Sino-French Hoffmann Institute, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China.
State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
FASEB J. 2024 Dec 15;38(23):e70211. doi: 10.1096/fj.202401237R.
Malaria remains a significant global public health problem. T follicular helper (Tfh) cells, a subset of CD4 T cells, have the capacity to regulate B cells, plasma cells, and antibody production, among other functions. Myeloid-derived suppressor cells (MDSCs) possess strong immunosuppressive abilities and can negatively regulate various immune responses. However, the role of MDSCs in inhibiting Tfh-cell responses during Plasmodium infection remains unclear. In this study, we investigated the regulatory effect of MDSCs on Tfh cell-mediated immune responses upon Plasmodium infection. We found that the numbers of MDSCs increased upon Plasmodium infection. Further mechanism study revealed that MDSC-derived Arg-1 and PD-L1 prevented Tfh cell proliferation and activation. Conversely, the addition of nor-NOHA or anti-PD-L1 monoclonal antibodies enhanced the proliferation and activation of Tfh cells, indicating that the inhibitory effect of MDSCs on Tfh cells was dependent on Arg-1 and PD-1/PD-L1. In vivo depletion of MDSCs enhanced Tfh-cell responses and antibody production, as well as relieved symptoms of infected mice and improved their survival rates. These findings provide insights into the immunosuppressive role of MDSCs in inhibiting Tfh cell immune responses and further impairing humoral immunity. Our study provides new strategies for malaria prevention and control.
疟疾仍然是一个重大的全球公共卫生问题。滤泡辅助性T（Tfh）细胞是CD4 T细胞的一个亚群，具有调节B细胞、浆细胞和抗体产生等多种功能。髓系来源的抑制性细胞（MDSCs）具有强大的免疫抑制能力，可对各种免疫反应产生负调节作用。然而，MDSCs在疟原虫感染期间抑制Tfh细胞反应中的作用仍不清楚。在本研究中，我们调查了MDSCs对疟原虫感染时Tfh细胞介导的免疫反应的调节作用。我们发现疟原虫感染后MDSCs数量增加。进一步的机制研究表明，MDSC来源的精氨酸酶-1（Arg-1）和程序性死亡受体配体1（PD-L1）可阻止Tfh细胞增殖和活化。相反，添加Nω-羟基-L-精氨酸（nor-NOHA）或抗PD-L1单克隆抗体可增强Tfh细胞的增殖和活化，这表明MDSCs对Tfh细胞的抑制作用依赖于Arg-1和程序性死亡受体1/程序性死亡受体配体1（PD-1/PD-L1）。体内清除MDSCs可增强Tfh细胞反应和抗体产生，并减轻感染小鼠的症状，提高其存活率。这些发现为MDSCs在抑制Tfh细胞免疫反应及进一步损害体液免疫方面的免疫抑制作用提供了见解。我们的研究为疟疾防控提供了新策略。
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