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

Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE

Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley
Original Publication: [Bethesda, Md.] : The Federation, [c1987-

Plasmodium yoelii*/immunology ; Malaria*/immunology ; Myeloid-Derived Suppressor Cells*/immunology ; T Follicular Helper Cells*/immunology ; B7-H1 Antigen*/immunology ; B7-H1 Antigen*/metabolism ; Mice, Inbred C57BL*; Animals ; Mice ; Female ; Programmed Cell Death 1 Receptor/metabolism ; Programmed Cell Death 1 Receptor/immunology ; Cell Proliferation ; Arginase/metabolism ; Lymphocyte Activation/immunology ; T-Lymphocytes, Helper-Inducer/immunology

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.
(© 2024 Federation of American Societies for Experimental Biology.)

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2022YFC2304205 MOST | National Key Research and Development Program of China (NKPs); 82471791 MOST | National Natural Science Foundation of China (NSFC); 82304574 MOST | National Natural Science Foundation of China (NSFC); A2024163 Medical scientific research foundation of Guangdong province; 202301-404 The open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University; Qingyuan People's Hospital; PX-66221466 Students' Innovation Ability Enhancement Plan project of Guangzhou Medical University; JCXKJS2021C08 Discipline Construction Fund of Guangzhou Medical University; GZNL2023A01009 major projects of guangzhou national laboratory; GZNL2024A01017 major projects of guangzhou national laboratory; 2024312082 Tertiary education scientific research project of Guangzhou Municipal Education Bureau

Keywords: Arg‐1; MDSCs; PD‐L1; Tfh cells; malaria

0 (B7-H1 Antigen)
0 (Programmed Cell Death 1 Receptor)
EC 3.5.3.1 (Arginase)
0 (Cd274 protein, mouse)
EC 3.5.3.1 (Arg1 protein, mouse)
0 (Pdcd1 protein, mouse)

Date Created: 20241204 Date Completed: 20241204 Latest Revision: 20241204

20241204

10.1096/fj.202401237R

39629706