TIM-1+ B Cells are more Efficient IL-10 Producers in Liver Fibrosis Caused by Alveolar Echinococcosis

Abstract

Background: The cestode Echinococcus multilocularis (E. multilocularis) infection, a serious health problem worldwide, causes alveolar echinococcosis (AE), a tumor-like disease predominantly located in the liver and able to spread to any organs. Until now, there have been few studies that explain how TIM-1+B cells contribute to the immune tolerance in E. multilocularis infection.Methods: Hematoxylin-eosin (H&E) and Masson staining were used to assess the pathological inflammatory changes and collagen deposition respectively in the liver of E. multilocularis infected mice. Desmin, TIM-1 and IL-10 were detected by immunohistochemistry (IHC). qRT-PCR and ELISA were used to detect the IL-10 of liver and serum, respectively. Flow cytometry was used to assess the level and function of CD19+TIM-1+ cells and CD19+CD5+CD1dhi cells in spleen. Immunofluorescence (IF) were used to detect the co-localization of immune cells in the liver.Results: At 180 days after infection, inflammatory cells and fibrosis could be observed in the liver of mice in the infection group, a large number of activated hepatic stellate cells (HSC) and TIM-1+ cells appeared around the lesion and the expression of IL-10 was also significantly higher than that in control group. The level and function of CD19+TIM-1+ cells and CD19+CD5+CD1dhi cells in the spleen were up-regulated in the infection group, but CD19+TIM-1+ cells produced IL-10 more efficiently and could be recruited to the lesion.Conclusions: In the late stage of alveolar echinococcosis, CD19+TIM-1+ cells can be recruited to the lesion and may be more efficient IL-10 producers to participate in the formation of immune tolerance.