Autophagy induced by Trichinella spiralis infection alleviate TNBS-induced colitis in mice through inhibiting the NLRP3 inflammasome

  • Microb Pathog. 2026 Jul:216:108526. doi: 10.1016/j.micpath.2026.108526.
Yanan Zhang  1 Yuxin Wang  2 Zhiyuan Zhang  3 Xuanrui Liu  4 Xinyi Kang  5 Wentao Yang  6 Xin Cao  7 Yanlong Jiang  8 Jianzhong Wang  9 Yan Zeng  10 Chunwei Shi  11 Haibin Huang  12 Chunfeng Wang  13 Guilian Yang  14 Jingwei Zhang  15 Nan Wang  16
Affiliations
  • 1. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 2. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 3. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 4. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 5. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 6. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 7. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 8. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 9. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 10. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 11. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 12. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 13. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 14. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 15. College of Foreign Languages, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
  • 16. College of Veterinary Medicine, Jilin Agricultural University, Changchun, 130118, China; Jilin Provincial Key Laboratory of Animal Microecology and Healthy Breeding, Jilin Agricultural University, Changchun, 130118, China; Engineering Research Center of Microecological Vaccines (Drugs) for Major Animal Diseases, Ministry of Education, Jilin Agricultural University, Changchun, 130118, China. Electronic address: [email protected].
Abstract

Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a group of chronic intestinal inflammatory disorders with diverse etiologies and limitations in current treatments. Trichinella spiralis, a foodborne parasitic nematode, has been reported to alleviate colitis in mouse models, but its specific mechanism remains unclear.

Methods: This study aims to investigate whether T. spiralis-induced Autophagy can alleviate IBD by inhibiting the NLRP3 inflammasome. Experimental colitis was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS) in mice 21 days after T. spiralis Infection. Experimental groups were treated with 3-methyladenine (3-MA, Autophagy inhibitor), rapamycin (Rapa, Autophagy activator), or MCC950 (NLRP3 Inhibitor), respectively. The severity of enteritis, the levels of Autophagy and NLRP3 inflammasome activity, were evaluated using colon length, body weight, disease activity index (DAI) scores, hematoxylin-eosin (H&E) staining, myeloperoxidase (MPO) activity assay, flow cytometry, qPCR, and Western blot.

Results: The results revealed that T. spiralis Infection alleviated colitis, concurrent with enhanced Autophagy and suppressed NLRP3 inflammasome activation. Notably, inhibition of Autophagy led to aggravated colitis symptoms and concomitant activation of the NLRP3 inflammasome. In contrast, Autophagy activation resulted in attenuated colitis manifestations and inhibition of the NLRP3 inflammasome. Moreover, direct inhibition of the NLRP3 inflammasome was capable of alleviating colitis.

Conclusions: This study reveals that T. spiralis can alleviate IBD by inducing Autophagy to inhibit the NLRP3 inflammasome, providing new insights into the treatment of IBD.

Keywords
Autophagy; IBD; NLRP3 inflammasome; Trichinella spiralis.
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