Deficiency of PKCλ/ι alleviates the liver pathologic impairment of Schistosoma japonicum infection by thwarting Th2 response

• Published in: Parasites & vectors Vol. 15; no. 1; p. 154
• Main Authors: Mei, Congjin, Yang, Yingying, Dong, Panpan, Song, Lijun, Zhou, Yonghua, Xu, Yongliang, Yu, Chuanxin
• Format: Journal Article
• Language: English
• Published: England BioMed Central 03.05.2022; BMC
• Subjects: Analysis; Animals; Bioengineering; Cell differentiation; Cell proliferation; Cytokines; Cytokines - metabolism; Defence mechanisms; Differentiation (biology); Eggs; Fibrosis; Flow cytometry; Fluorescence; Genotype & phenotype; Granuloma; Granulomas; Helper cells; HMGB1 protein; Immune response; Immune system; Immunity; Infections; Inflammation; Interleukin 4; Isoenzymes - genetics; Isoenzymes - metabolism; Kinases; Laboratory animals; Lesions; Liver; Liver Cirrhosis; Liver Diseases; Liver fibrosis; Lymphocytes T; Metabolism; Mice; Mice, Knockout; Nucleotide sequence; Parasitic diseases; PCR; PKCλ/ι; Proliferation; Protein Kinase C - genetics; Protein Kinase C - metabolism; Proteins; Schistosoma japonicum; Schistosomiasis; Schistosomiasis japonica - immunology; Secretion; Secretions; Spleen; Th2 polarization; Transforming growth factor-b1; Switzerland; China; Granuloma; Liver fibrosis; PKCλ/ι; Schistosoma japonicum; Th2 polarization
• ISSN: 1756-3305; 1756-3305
• DOI: 10.1186/s13071-022-05283-x

The activation of immune response driven by the eggs of Schistosoma japonicum and the subsequent secretions is the culprit behind granulomatous inflammation and liver fibrosis. Evidence suggests that PKCλ/ι participates in a variety of physiological and pathological processes, including the regulation of metabolism, growth, proliferation and differentiation of cells. However, the role of PKCλ/ι in liver disease caused by Schistosoma japonicum remains unclear. In the present study, we observe the pathological changes of egg-induced granulomatous inflammation and fibrosis in the liver of mice infected by Schistosoma japonicum by using conditional PKCλ/ι-knockout mice and wild-type control. Immune cytokines and fibrogenic factors were analyzed by performing flow cytometry and real-time fluorescence quantitative PCR. The results of H&E and Masson staining show that the degree of granulomatous lesions and fibrosis in the liver of the infected PKCλ/ι-knockout mice was significantly reduced compared with those of the infected wild-type mice. The mean area of single granuloma and hepatic fibrosis in the PKCλ/ι-knockout mice was significantly lower than that of the wild-type mice (85,295.10 ± 5399.30 μm vs. 1,433,702.04 ± 16,294.01 μm , P < 0.001; 93,778.20 ± 8949.05 μm vs. 163,103.01 ± 11,103.20 μm , P < 0.001), respectively. Serological analysis showed that the ALT content was significantly reduced in the infected knockout mice compared with infected wild-type mice. RT-PCR analysis showed that IL-4 content in knockout mice was significantly increased after Schistosoma japonicum infection, yet the increase was less than that in infected wild-type mice (P < 0.05). PKCλ/ι deficiency led to reduced expression of fibrosis-related factors, including TGF-β1, Col-1, Col-3, α-SMA and liver DAMP factor HMGB1. Flow cytometry analysis showed that the increasing percentage of Th2 cells, which mainly secrete IL-4 cytokines in spleen cells, was significantly lower in PKCλ/ι-deficient mice compared with wild-type mice after infection (P < 0.05). Our data demonstrate that PKCλ/ι deficiency alleviating granulomatous inflammation and fibrosis in the liver of mice with S. japonicum infection by downregulating Th2 immune response is the potential molecular mechanism behind the role of PKCλ/ι in schistosomiasis.