期刊
CELLULAR IMMUNOLOGY
卷 362, 期 -, 页码 -出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.cellimm.2021.104303
关键词
Trichinella spiralis; Cystatin; STAT4; Macrophage; IL-12; T-bet; IFN-gamma; Myotubule; L1 larval stage
资金
- Mahidol University
- Thailand Research Fund through a Royal Golden Jubilee Ph.D. scholarship [PHD/0209/2559]
- Newton Foundation
- University of Liverpool Welcome Trust ISSF
This study investigated the impact of TsCstN derived from Trichinella spiralis L1 stage on macrophage-T cell interaction and immune responses. The results showed that TsCstN negatively regulated IFN-gamma production in macrophages, but not IL-17A, as well as affected IL-12 levels and the autonomous response in myotubule cells. This work reveals a potential pathway for L1 larvae to evade immune responses and establish infection.
We have previously identified a cystatin, TsCstN, derived from the L1 stage of Trichinella spiralis and have shown that this protein is internalised in macrophages. Here we sought to address if this macrophage-TsCstN interaction could alter downstream T-cell priming. Using LPS-primed macrophages to stimulate T-cells in a co-culture system with or without TsCstN we assessed the resultant T-cell outcomes. IFN-gamma, both protein and mRNA, but not IL-17A was negatively regulated by inclusion of TsCstN during macrophage priming. We identified a cell-cell contact independent change in the levels of IL-12 that led to altered phosphorylated STAT4 levels and translocation. TsCstN also negatively regulated the autonomous response in the myotubule cell line, C2C12. This work identifies a potential pathyway for L1 larvae to evade protective Th1 based immune responses and establish muscle-stage T. spiralis infection.
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