RESUMO
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.
Assuntos
Interferon gama/metabolismo , Fator de Transcrição STAT4/metabolismo , Trichinella spiralis/metabolismo , Animais , Cistatinas/metabolismo , Cistatinas/farmacologia , Citocinas/metabolismo , Feminino , Interferon gama/fisiologia , Interleucina-12/imunologia , Interleucina-12/metabolismo , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fator de Transcrição STAT4/fisiologia , Transdução de Sinais , Linfócitos T/metabolismo , Trichinella spiralis/genética , Trichinella spiralis/imunologiaRESUMO
Toxoplasma gondii and Cryptosporidium spp. can cause devastating pathological effects in humans and livestock, and in particular to young or immunocompromised individuals. The current treatment plans for these enteric parasites are limited due to long drug courses, severe side effects or simply a lack of efficacy. The study of the early interactions between the parasites and the site of infection in the small intestinal epithelium has been thwarted by the lack of accessible, physiologically relevant and species-specific models. Increasingly, 3D stem cell-derived enteroid models are being refined and developed into sophisticated models of infectious disease. In this review, we shall illustrate the use of enteroids to spearhead research into enteric parasitic infections, bridging the gap between cell line cultures and in vivo experiments.