Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice

Abstracts: Background: Autoimmune hepatitis (AIH) is a chronic progressive liver disease caused by the immune system mistakenly attacking its own hepatocytes. The role of the gut microbiome in the pathogenesis and progression of AIH is of considerable significance. However, the dearth of suitable a...

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Main Authors: Liqi Zhu, Yuanyuan Liang, Linghan Yang, Qihui Yang, Jun Yin, Tao Wang, Xiangming Xu, Quan Zhang
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Journal of Translational Autoimmunity
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589909025000103
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author Liqi Zhu
Yuanyuan Liang
Linghan Yang
Qihui Yang
Jun Yin
Tao Wang
Xiangming Xu
Quan Zhang
author_facet Liqi Zhu
Yuanyuan Liang
Linghan Yang
Qihui Yang
Jun Yin
Tao Wang
Xiangming Xu
Quan Zhang
author_sort Liqi Zhu
collection DOAJ
description Abstracts: Background: Autoimmune hepatitis (AIH) is a chronic progressive liver disease caused by the immune system mistakenly attacking its own hepatocytes. The role of the gut microbiome in the pathogenesis and progression of AIH is of considerable significance. However, the dearth of suitable animal models has significantly constrained advancements in the pathogenesis and the development of therapeutic strategies for AIH. Helicobacter mastomyrinus (H. mastomyrinus, Hm) is a potentially zoonotic pathogenic microorganism capable of causing diseases of the enterohepatic system in rodent laboratory animals. Nevertheless, research on its role and mechanisms in causing liver disease is severely limited. Methods: In this study, male BALB/c mice were infected with Hm isolate Hm-17, and were sacrificed at 4 w, 8 w, 14 w and 22 w after infection, respectively. The serum was collected for detecting a number of AIH indicators, including the aminotransferases level, IgG content and autoantibody level. Additionally, the liver tissue was examined for pathological analysis, fibrosis, bacterial content, and the distribution of immune cells. Results: It was observed that the infection initially caused focal necrotizing hepatitis and subsequently progressed to interface hepatitis with lymphocyte/plasma cell infiltration, as well as hypergammaglobulinemia and autoantibody reactions, predominantly to Anti-nuclear and anti-smooth muscle antibodies. Furthermore, as the infection persisted, the mice exhibited a progressive increase in liver fibrosis and mild steatosis. Despite the maintenance of a low level of Hm colonization in the liver, there was a notable infiltrate of macrophages, T and B lymphocytes. In particular, the inflammatory foci in the Hm-infected liver were highly enriched for IL17+ cells. Conclusion: The present study provides an animal model of immunological liver injury induced by Hm infection that exhibits main characteristics similar to those observed in AIH-1 patients. This model may serve as a novel animal model for the study of the pathogenesis and potential therapeutic strategies for human AIH.
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spelling doaj-art-e2f4d8d214904a97b5323bdc04e20a912025-02-03T04:16:52ZengElsevierJournal of Translational Autoimmunity2589-90902025-06-0110100275Helicobacter mastomyrinus infection induces autoimmune hepatitis in miceLiqi Zhu0Yuanyuan Liang1Linghan Yang2Qihui Yang3Jun Yin4Tao Wang5Xiangming Xu6Quan Zhang7College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, ChinaCollege of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Taizhou University, Taizhou, China; Corresponding author. Taizhou University, Taizhou, China.College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, China; International Research Laboratory of Prevention and Control of Important Animal Infectious Diseases and Zoonotic Diseases of Jiangsu Higher Education Institutions, Yangzhou University, Yangzhou, China; Corresponding author. College of Veterinary Medicine, Institute of Comparative Medicine, Yangzhou University, Yangzhou, China.Abstracts: Background: Autoimmune hepatitis (AIH) is a chronic progressive liver disease caused by the immune system mistakenly attacking its own hepatocytes. The role of the gut microbiome in the pathogenesis and progression of AIH is of considerable significance. However, the dearth of suitable animal models has significantly constrained advancements in the pathogenesis and the development of therapeutic strategies for AIH. Helicobacter mastomyrinus (H. mastomyrinus, Hm) is a potentially zoonotic pathogenic microorganism capable of causing diseases of the enterohepatic system in rodent laboratory animals. Nevertheless, research on its role and mechanisms in causing liver disease is severely limited. Methods: In this study, male BALB/c mice were infected with Hm isolate Hm-17, and were sacrificed at 4 w, 8 w, 14 w and 22 w after infection, respectively. The serum was collected for detecting a number of AIH indicators, including the aminotransferases level, IgG content and autoantibody level. Additionally, the liver tissue was examined for pathological analysis, fibrosis, bacterial content, and the distribution of immune cells. Results: It was observed that the infection initially caused focal necrotizing hepatitis and subsequently progressed to interface hepatitis with lymphocyte/plasma cell infiltration, as well as hypergammaglobulinemia and autoantibody reactions, predominantly to Anti-nuclear and anti-smooth muscle antibodies. Furthermore, as the infection persisted, the mice exhibited a progressive increase in liver fibrosis and mild steatosis. Despite the maintenance of a low level of Hm colonization in the liver, there was a notable infiltrate of macrophages, T and B lymphocytes. In particular, the inflammatory foci in the Hm-infected liver were highly enriched for IL17+ cells. Conclusion: The present study provides an animal model of immunological liver injury induced by Hm infection that exhibits main characteristics similar to those observed in AIH-1 patients. This model may serve as a novel animal model for the study of the pathogenesis and potential therapeutic strategies for human AIH.http://www.sciencedirect.com/science/article/pii/S2589909025000103Helicobacter mastomyrinusAutoimmune hepatitisAnimal modelAIH-1IL17
spellingShingle Liqi Zhu
Yuanyuan Liang
Linghan Yang
Qihui Yang
Jun Yin
Tao Wang
Xiangming Xu
Quan Zhang
Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
Journal of Translational Autoimmunity
Helicobacter mastomyrinus
Autoimmune hepatitis
Animal model
AIH-1
IL17
title Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
title_full Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
title_fullStr Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
title_full_unstemmed Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
title_short Helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
title_sort helicobacter mastomyrinus infection induces autoimmune hepatitis in mice
topic Helicobacter mastomyrinus
Autoimmune hepatitis
Animal model
AIH-1
IL17
url http://www.sciencedirect.com/science/article/pii/S2589909025000103
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