Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-γ-activated MSC through modulating Th1/Th2 responses

作者：Chao Liu, Yishu Zhang, Fang Chen, Xiaoying Wu, Bei-bei Zhang, Zhongdao Wu, Junxia Lei · 发表于：Stem Cell Research & Therapy · 年份：2020 · DOI：10.1186/s13287-020-01735-2 · 被引用次数：27 · 研究领域：Parasites and Host Interactions、Liver physiology and pathology、Immune responses and vaccinations

Abstract Background and aims A marked egg-induced CD4 + T cell programmed inflammation and subsequent hepatic fibrosis characterize the pathogenesis of schistosomiasis. Mesenchymal stem cell (MSC) has been extensively studied for the treatment of schistosomiasis. However, the mechanism by which MSCs modulate the pathogenesis of schistosomiasis has not been clarified. Furthermore, the local inflammatory milieu may greatly influence the immunoregulatory properties of MSCs, and our early experiments demonstrated that Toll-like receptor (TLR)2/TLR4 agonist effected immune modulation of MSC. Here, we further investigated their modulation on the pathogenesis of schistosomiasis. Methods Adult BALB/c male mice were percutaneously infected with 16 ± 2 pairs S. japonicum cercariae and received intravenously pretreated MSC at 1 week and 3 weeks post-infection, respectively. At 8 weeks post-infection, effects of MSC on liver histology were shown by hematoxylin and eosin (H&E) staining and Masson staining and quantitatively compared by the hepatic hydroxyproline content; α-smooth muscle actin (α-SMA), collagen type I(Col-1), transforming growth factor β (TGF-β), and tumor necrosis factor-α (TNF-α) gene expression in the liver were assessed by semi-quantitative polymerase chain reaction (PCR); the Th1/Th2 dominance among different groups was compared by analyzing CD4 + interferon-γ (IFN-γ)+ and CD4+interleukin-4 (IL-4)+T cells in the liver by flow cytometry and serum level of IFN-γ and...