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

被引:0
作者
Mo, Lengshan [1 ,2 ]
Hong, Cansheng [2 ]
Jiang, Zhihan [2 ]
Zhu, Yiqiang [3 ,4 ]
Zhou, Lu [2 ]
Tan, Simin [2 ]
Deng, Guorong [2 ]
Qi, Yanwei [2 ]
Hu, Tengfei [2 ]
Wu, Qianlian [1 ]
Zhao, Yi [2 ]
Qiu, Huaina [2 ]
Liang, Taizhen [3 ,4 ]
Lin, Peibin [5 ]
Zhang, Jian [6 ]
Ma, Xiancai [3 ,4 ]
Yang, Quan [1 ,2 ,5 ]
机构
[1] Guangzhou Med Univ, Sino French Hoffmann Inst, Sch Basic Med Sci, Dept Pathogen Biol & Immunol, Guangzhou, Peoples R China
[2] Guangzhou Med Univ, Affiliated Hosp 2, State Key Lab Resp Dis, Guangdong Prov Key Lab Allergy & Clin Immunol, Guangzhou, Peoples R China
[3] Guangzhou Med Univ, Guangzhou Inst Resp Hlth, Natl Clin Res Ctr Resp Dis, State Key Lab Resp Dis,Affiliated Hosp 1, Guangzhou, Peoples R China
[4] Guangzhou Int Bio Isl, Guangzhou Natl Lab, Guangzhou, Peoples R China
[5] Guangzhou Med Univ, Affiliated Qingyuan Hosp, Qingyuan Peoples Hosp, Qingyuan, Peoples R China
[6] Guangzhou Med Univ, Sch Basic Med Sci, Dept Biomed Engn, Guangzhou, Peoples R China
关键词
Arg-1; malaria; MDSCs; PD-L1; Tfh cells; IMMUNITY; MALARIA; MDSC; DIFFERENTIATION; EXPANSION; HEMOZOIN; CHABAUDI;
D O I
10.1096/fj.202401237R
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:22
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