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Type I/II Immune Balance Contributes to the Protective Effect of AIF-1 on Hepatic Immunopathology Induced by Schistosoma japonicum in a Transgenic Mouse Model

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Abstract

Schistosomiasis is the second most debilitating neglected tropical disease in the world. Liver egg granuloma and fibrosis are the main damage of schistosomiasis. In this study, the role of allograft inflammatory factor-1 (AIF-1) in liver pathology and its regulation in immune responses were investigated in a transgenic mouse infected with Schistosoma japonicum. We found that AIF-1 overexpression reduced worm burden and decreased egg granuloma sizes and serum alanine aminotransferase levels, along with inhibited hepatic collagen deposition and serum hydroxyproline levels during S. japonicum infection. Moreover, AIF-1 overexpression resulted in an increased ratio of Th1/Th2, increased levels of IFN-γ and T-bet, and lower levels of GATA-3 in the spleen, accompanied by increased M1 percentages, decreased M2 percentages, and thus a higher ratio of M1/M2 in the peritoneal cavity and liver. AIF-1 induced CD68 and iNOS mRNA expression and protein levels of cytoplasmic p-P38 and nuclear NF-κB, along with enhanced levels of TNF-α and TGF-β in macrophages in vitro. Moreover, the hepatic pathology had a negative correlation with Th1/Th2 and M1/M2 ratios in the infected mice. The findings reveal that the beneficial role of AIF-1 in alleviating hepatic damage is related to restoring type I/II immune balance in S. japonicum infection.

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Acknowledgements

We would like to sincerely appreciate Professor Zhengwang Chen from College of Life Science and Technology, Huazhong University of Science and Technology, for the kind gift of recombination protein of AIF-1.

Funding

This work was supported by the National Nature Science Foundation of China (grants 81772220 to Jiahui Lei and 81201310 to Fei Guan).

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Authors and Affiliations

  1. Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Jiahui Lei, Wenwen Zheng, Mwadini Khamis, Jinyuan Zhang & Fei Guan

  2. Department of Clinical Laboratory, First Affiliated Hospital of Air Force Medical University, Xi’an, 710032, China

    Yujie Feng

  3. Department of Clinical Laboratory, General Hospital of Central Theater Command, Wuhan, 430000, China

    Xiao Hou

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  1. Jiahui Lei
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Contributions

Conceptualization, methodology, data curation, analysis, and manuscript-original draft preparation were performed by Jiahui Lei. The methodology, data curation and analysis were performed by Yujie Feng, Wenwen Zheng, Mwadini Khamis, and Jinyuan Zhang. The analysis was completed by Xiao Hou. Fei Guan performed the conceptualization, data curation, analysis, manuscript-original draft preparation, reviewing and editing, and supervision. All authors read and approved the previous and final manuscript.

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Correspondence to Fei Guan.

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All animal experiments were in accordance with the regulations of the Animal Care and Use Committee of Tongji Medical College, Huazhong University of Science and Technology (SCXK2020-0001). Experiments on animal infection and sacrifice were carried out under anesthesia.

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Lei, J., Feng, Y., Zheng, W. et al. Type I/II Immune Balance Contributes to the Protective Effect of AIF-1 on Hepatic Immunopathology Induced by Schistosoma japonicum in a Transgenic Mouse Model. Inflammation (2024). https://doi.org/10.1007/s10753-024-02010-9

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