旋毛虫排泄/分泌抗原通过减轻炎症和促进紧密连接来改善猪流行性腹泻病毒诱导的猪肠道类器官黏膜损伤。

Trichinella spiralis excretory/secretory antigens ameliorate porcine epidemic diarrhea virus-induced mucosal damage in porcine intestinal oganoids by alleviating inflammation and promoting tight junction.

作者信息

Liu Yinju, Tan Jinlong, Zhang Nianzhang, Qu Zigang, Li Wenhui, Wu Yaodong, Yin Hong, Liu Guangliang, Fu Baoquan

机构信息

State Key Laboratory for Animal Disease Control and Prevention, Key Laboratory of Veterinary Parasitology of Gansu Province, Gansu Province Research Center for Basic Disciplines of Pathogen Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.

出版信息

Int J Parasitol. 2025 Mar;55(3-4):183-195. doi: 10.1016/j.ijpara.2024.12.002. Epub 2024 Dec 25.

DOI:10.1016/j.ijpara.2024.12.002

PMID:39725260

Abstract

Trichinella spiralis and porcine epidemic diarrhea virus (PEDV) are two infectious swine pathogens. Parasite excretory/secretory antigens play critical roles in various disease processes. To explore the coexistence mechanism of two pathogens infecting the same host, the intestinal organoid was utilized to reproduce these biological processes. In this study, we investigated the effects of T. spiralis excretory/secretory antigens (TsES) on PEDV-induced inflammatory regulation, lesion recovery, and mucosal barrier repair in porcine intestinal organoids. The results showed that PEDV effectively infected the porcine intestinal organoids. Next, TsES inhibited pro-inflammatory cytokines and increased the anti-inflammatory cytokines produced by PEDV-infected porcine intestinal organoids. Further, four-dimensional (4D) label-free quantitative proteomics and western blotting confirmed that TsES regulate the inflammation caused by PEDV infection through the nuclear factor kappa-B (NF-κB) pathway. In addition, TsES promoted cell proliferation, inhibited apoptosis, and reduced PEDV-induced lesions in intestinal organoids. The elevated secretory immunoglobulin A (sIgA) levels caused by PEDV infection were downregulated by TsES treatment in intestinal organoids. TsES treatment reversed the mucosal barrier damage caused by PEDV infection in intestinal organoids. Finally, PEDV replication increased after TsES treatment in organoids. We highlight the potential of TsES to ameliorate PEDV-induced inflammation, mucosal lesions, and barrier damage in porcine intestinal organoids. TsES also contribute to PEDV replication. This study presents a novel research model for research on host-virus-parasite interactions, while also providing a theoretical foundation to consider parasite derivatives as a potential adjunctive therapy for intestinal inflammation.

摘要

旋毛虫和猪流行性腹泻病毒（PEDV）是两种感染猪的病原体。寄生虫排泄/分泌抗原在各种疾病过程中起着关键作用。为了探究两种病原体感染同一宿主的共存机制，利用肠道类器官重现这些生物学过程。在本研究中，我们调查了旋毛虫排泄/分泌抗原（TsES）对PEDV诱导的猪肠道类器官炎症调节、损伤恢复和黏膜屏障修复的影响。结果表明，PEDV能有效感染猪肠道类器官。接下来，TsES抑制促炎细胞因子，并增加PEDV感染的猪肠道类器官产生的抗炎细胞因子。此外，二维液相色谱-质谱联用（4D）无标记定量蛋白质组学和蛋白质印迹法证实，TsES通过核因子κB（NF-κB）途径调节PEDV感染引起的炎症。此外，TsES促进细胞增殖，抑制细胞凋亡，并减少PEDV诱导的肠道类器官损伤。在肠道类器官中，TsES处理下调了PEDV感染引起的分泌型免疫球蛋白A（sIgA）水平升高。TsES处理逆转了PEDV感染引起的肠道类器官黏膜屏障损伤。最后在类器官中，TsES处理后PEDV复制增加。我们强调了TsES减轻PEDV诱导的猪肠道类器官炎症、黏膜损伤和屏障损伤的潜力。TsES也有助于PEDV复制。本研究为宿主-病毒-寄生虫相互作用的研究提供了一种新的研究模型，同时也为将寄生虫衍生物作为肠道炎症的潜在辅助治疗方法提供了理论基础。