2. Academic Validation
  3. Trichinella spiralis serine protease inhibitors regulate the dynamic interaction between endoplasmic reticulum stress and autophagy in host intestinal epithelial cells

Trichinella spiralis serine protease inhibitors regulate the dynamic interaction between endoplasmic reticulum stress and autophagy in host intestinal epithelial cells

  • Int Immunopharmacol. 2025 Aug 28:161:115005. doi: 10.1016/j.intimp.2025.115005.
Jingbo Zhen 1,  Feng Sun 1,  Xueting Liu 1,  Yuqi Yang 1,  Qiankun Li 1,  Qi Zhang 1,  Yang Han 1,  Zhixin Li 1,  Lihao Lin 1,  Yixin Lu 2,  Shuo Jia 3
Affiliations

Affiliations

  • 1 Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Street, Harbin 150030, China.
  • 2 Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Street, Harbin 150030, China. Electronic address: luyixin@neau.edu.cn.
  • 3 Heilongjiang Provincial Key Laboratory of Zoonosis, College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Street, Harbin 150030, China. Electronic address: jiashuo@neau.edu.cn.
PMID: 40505235 DOI: 10.1016/j.intimp.2025.115005
Abstract

Endoplasmic reticulum stress (ERS) and Autophagy play key roles in host defense against pathogen invasion, but Trichinella spiralis (T. spiralis) can facilitate parasitism by escaping host defense. In this T. spiralis-host interaction, the regulation of T. spiralis and its excretory-secretory products on ERS-autophagy interaction remains unclear. Therefore, based on the fact that T. spiralis Infection can activate ERS and Autophagy in host intestinal epithelial cells (IECs), this study focused on the role of two T. spiralis serine Protease Inhibitors (TsSPIs) in the ERS-autophagy interaction. Firstly, the ERS-related indicators of mouse jejunum and porcine's IECs were significantly changed after TsSPIs stimulation. The specific localization of immunoglobulin heavy chain binding protein (BIP) in IECs indicated that TsSPIs could induce IECs ERS. Next, after inhibiting ERS and the key proteins of unfolded protein response (UPR) pathway, it was found that the expression of autophagy-related indicators and the formation of autophagosomes were inhibited, confirming that TsSPIs-induced Autophagy was ERS-dependent and mediated by the UPR pathway. Finally, the results showed that the expression of ERS-related indicators was up-regulated after inhibiting Autophagy, indicating that TsSPIs-induced Autophagy negatively regulated ERS. In conclusion, T. spiralis-secreted TsSPIs induced ERS after entering IECs, ERS promoted Autophagy through the UPR pathway, and Autophagy negative feedback regulated ERS to restore IECs homeostasis. This dynamic balance between ERS-regulated host cell homeostasis imbalance and autophagy-dependent homeostasis reconstruction induced by TsSPIs was conducive to Parasite parasitism.

Keywords

ERS-autophagy interaction; Intestinal epithelial cells; Serine protease inhibitors; Trichinella spiralis.

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