C5a/C5aR信号在微小隐孢子虫感染中的免疫调节作用研究

doi:10.11843/j.issn.0366-6964.2022.08.020

Abstract

Abstract: The aim of this study was to explore the regulation of C5a/C5aR signal in the immune response of host CD4⁺ T cell during Cryptosporidium parvum infection. We have utilized C. parvum as the research object, and selected BALB/c suckling mice and C5aR inhibited BALB/c suckling mice as infection models. The expression level of C5aR in the ileum tissues of BALB/c suckling mice was detected by using real-time PCR and immunohistochemistry. The expression patterns of C. parvum HSP70 gene and main effector cytokines (IFN-γ, IL-4, IL-17 and TGF-β) of CD4⁺ T cell subsets (Th1, Th2, Th17 cells and Treg cells) were analyzed by real-time PCR. The injury of ileal mucosa in suckling mice was observed by histopathology analysis. Compared with mice in the control group, C. parvum infection could significantly increase the expression levels of C5aR mRNA and protein (P<0.05), as well as IFN-γ in the ileum tissues of suckling mice (P<0.05). Compared with mice infected with C. parvum, the expression levels of main effector cytokines of Th1, Th2 and Treg cells, namely IFN-γ, IL-4 and TGF-β, significantly reduced in C5aR inhibited BALB/C suckling mice infected with C. parvum (P<0.05), and the expression level of IL-17, the main effector cytokine of Th17 cells, significantly increased in suckling mice treated with C5aR inhibitor (P<0.05). Histopathology analysis of ileal mucosa in suckling mice indicated inhibition of C5aR could significantly improve the changes of villus diameter and mucosal thickness of ileum caused by C. parvum infection (P<0.05), but not for the villus length and the ratio of villus length to crypt depth. Analysis of the mRNA level for Cryptosporidium HSP70 gene showed that inhibition of C5aR could significantly affect the proliferation of C. parvum in ileum (P<0.05). C5a/C5aR signal may participate in the process of interaction between host and Cryptosporidium by dynamically regulating the expression of major effector cytokines for CD4⁺ T cell subsets, providing reference basis for further understanding the interaction mechanism between Cryptosporidium spp. and host.

Key words: Cryptosporidium parvum, BALB/c sucking mouse, C5a/C5aR signal, CD4⁺ T cell subsets, regulation

CLC Number:

WU Xuemei, YANG Xin, YUAN Yajie, YIN Yanling, LAI Peng, SONG Junke, SHI Huaiping, ZHAO Guanghui. Immunomodulatory Effect of C5a/C5aR Signal during Cryptosporidium parvum Infection[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(8): 2621-2632.

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Immunomodulatory Effect of C5a/C5aR Signal during Cryptosporidium parvum Infection

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