Trichinella spiralis cystatin, TsCstN, modulates STAT4/IL-12 to specifically suppress IFN-γ production

Porntida Kobpornchai, Ellen Alana Tiffney, Poom Adisakwattana, Robin J. Flynn

Research output: Contribution to journalArticlepeer-review

Abstract

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-γ, 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.

Original languageEnglish
Article number104303
JournalCellular Immunology
Volume362
DOIs
Publication statusPublished - Apr 2021
Externally publishedYes

Keywords

  • Cystatin
  • IFN-γ
  • IL-12
  • L1 larval stage
  • Macrophage
  • Myotubule
  • STAT4
  • T-bet
  • Trichinella spiralis

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