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FASEB Journal

FASEB Journal

IF: 4.4
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Myeloid‐derived suppressor cells inhibit responses of T follicular helper cells during experimental Plasmodium yoelii infection

Published:4 December 2024 DOI: 10.1096/fj.202401237R
Lengshan Mo, Cansheng Hong, Zhihan Jiang, Yiqiang Zhu, Lu Zhou, Simin Tan, Guorong Deng, Yanwei Qi, Tengfei Hu, Qianlian Wu, Yi Zhao, Huaina Qiu, Taizhen Liang, Peibin Lin, Jian Zhang, Xiancai Ma, Quan Yang

Abstract

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.

Substances (5)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Dimethyl sulfoxide 67-68-5 C2H6OS 1924 suppliers $5.00-$120900.00
Brefeldin A 20350-15-6 C16H24O4 329 suppliers $23.00-$2395.30
5(6)-(N-SUCCINIMIDYLOXYCARBONYL)-3',6',O,O'-DIACETYLFLUORESCEIN 150347-59-4 C29H19NO11 238 suppliers $23.00-$2200.00
IONOMYCIN 56092-81-0 C41H72O9 203 suppliers $44.00-$6400.00
FETUIN 9014-81-7 NULL 92 suppliers $37.07-$4810.00

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