We established a mouse model of Schistosoma japonicum infection in order to study the effects of the infection on hepatocyte autophagy and apoptosis. We also stimulated HepG2 cells with soluble egg antigens (SEA) in vitro. At two, four, and six weeks post-infection, quantitative real-time PCR and Western blot (WB) were used to detect liver expression levels of autophagy and apoptosis-related proteins. HepG2 cells were treated with different concentrations of SEA. The changes in the levels of autophagy-related proteins and HepG2 cell apoptosis were detected. The Lc3b, Beclin1, Atg7, and Atg12 mRNA levels were significantly lower at four and six weeks after infection than those in the uninfected group. At four and six weeks following infection, the levels of Beclin1, LC3BII/I, Atg7, and p62 proteins were considerably lower than those in the uninfected group. The protein levels of pro-apoptotic Bax and cleaved caspase 3 and fibrosis-related proteins α-SMA and collagen 3 in the liver post-infection were significantly higher than those in uninfected mice. HepG2 cells stimulated with SEA showed decreased levels of Beclin1, p62, and Atg7 proteins and significantly increased apoptosis rates. The findings demonstrated that following infection with S. japonicum, mice’s liver fibrosis worsened, hepatic autophagy was suppressed, and hepatocyte apoptosis was encouraged.

Schistosoma japonicum eggs in the host liver form granuloma and liver fibrosis and then lead to portal hypertension and cirrhosis, seriously threatening human health. Natural killer (NK) cells can kill activated hepatic stellate cells (HSCs) against hepatic fibrosis. We used single-cell sequencing to screen hepatic NK cell subsets against schistosomiasis liver fibrosis. Hepatic NK cells were isolated from uninfected mice and mice infected for four and six weeks. The NK cells underwent single-cell sequencing. The markers’ expression in the NK subsets was detected through Reverse Transcription–Quantitative PCR (RT-qPCR). The proportion and granzyme B (Gzmb) expression of the total NK and Thy1⁺NK were detected. NK cells overexpressing Thy1 (Thy1-OE) were constructed, and functions were detected. The results revealed that the hepatic NK cells could be divided into mature, immature, regulatory-like, and memory-like NK cells and re-clustered into ten subsets. C3 (Cx3cr1⁺NK) and C4 (Thy1⁺NK) increased at week four post-infection, and other subsets decreased continuously. The successfully constructed Thy1-OE NK cells had significantly higher effector molecules and induced greater HSC apoptosis than the control NK cells. It revealed a pattern of hepatic NK cells in a mouse model of schistosomiasis. The Thy1⁺NK cells could be used as target cells against hepatic fibrosis.

Schistosomiasis japonica is a zoonotic parasitic disease causing liver fibrosis. Liver sinusoidal endothelial cells (LSECs) exhibit fenestrations, which promote hepatocyte regeneration and reverses the process of liver fibrosis. To investigate the pathological changes of LSECs in schistosomiasis, we established a Schistosomiasis model. The population, phenotype, and secretory function of LSECs were detected by flow cytometry at 20, 28, and 42 days post infection. The changes in LSEC fenestration and basement membrane were observed through scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Quantitative real-time PCR and Western blotting were used to detect the expression of molecules associated with epithelial–mesenchymal transition (EMT) and fibrosis of LSECs and the liver. The flow cytometry results showed that the total LSEC proportions, differentiated LSEC proportions, and nitric oxide (NO) secretion of LSECs were decreased, and the proportion of dedifferentiated LSECs increased significantly post infection. The electron microscopy results showed that the number of fenestrate was decreased and there was complete basement membrane formation in LSECs following infection. The qPCR and Western blot results showed that EMT, and fibrosis-related indicators of LSECs and the liver changed significantly during the early stages of infection and were aggravated in the middle and late stages. The pathological changes in LSECs may promote EMT and liver fibrosis induced by Schistosoma japonicum infection.