Myeloid‐derived suppressor cells inhibit responses of T follicular helper cells during experimental Plasmodium yoelii infection

• Published in: The FASEB journal 2024-12, Vol.38 (23), p.e70211-n/a
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Animals; Arginase - metabolism; Arg‐1; B7-H1 Antigen - immunology; B7-H1 Antigen - metabolism; Cell Proliferation; Female; Lymphocyte Activation - immunology; malaria; Malaria - immunology; MDSCs; Mice; Mice, Inbred C57BL; Myeloid-Derived Suppressor Cells - immunology; PD‐L1; Plasmodium yoelii - immunology; Programmed Cell Death 1 Receptor - immunology; Programmed Cell Death 1 Receptor - metabolism; T Follicular Helper Cells - immunology; T-Lymphocytes, Helper-Inducer - immunology; Tfh cells
• ISSN: 0892-6638; 1530-6860; 1530-6860
• 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. The expansion of myeloid‐derived suppressor cells (MDSCs) induced by Plasmodium yoelii infection inhibits the proliferation and activation of T follicular helper cells in the host immune system through increased expression of arginase 1 (Arg‐1) and PD‐L1, thereby impacting the differentiation of germinal center B cells into plasma cells for antibody production, highlighting the crucial role of MDSCs in regulating immune responses during malaria infection.