IL-17A-producing γδT cells promote liver pathology in acute murine schistosomiasis

Abstract

Background: The main symptoms of schistosomiasis are granuloma and fibrosis, caused by Schistosoma eggs. Numerous types of cells and cytokines are involved in the progression of Schistosoma infection. As a class of innate immune cells, γδT cells play critical roles in the early immune response. However, their role in modulating granuloma and fibrosis remains to be clarified. Methods: Liver fibrosis in wild-Type (WT) mice and T cell receptor (TCR) δknockout (KO) mice infected with Schistosoma japonicum was examined via Masson's trichrome staining of collagen deposition and quantitative reverse transcriptase-PCR (RT-PCR) of fibrosis-related genes. Granuloma was detected by hematoxylin-eosin (H&E) staining and quantified. Flow cytometry was used for immune cell profiling and for detecting cytokine secretion. The abundance of the related cytokines was measured using quantitative RT-PCR. Results: The livers of S. japonicum-infected mice had significantly increased proportions of interleukin (IL)-17A producing γδT cells and secreted IL-17A. Compared with the WT mice, TCR δdeficiency resulted in reduced pathological impairment and fibrosis in the liver and increased survival in infected mice. In addition, the profibrogenic effects of γδT cells in infected mice were associated with enhanced CD11b+Gr-1+ cells, concurrent with increased expression of transforming growth factor (TGF)-β in the liver. Conclusions: In this mouse model of Schistosoma infection, γδT cells may promote liver fibrosis by recruiting CD11b+Gr-1+ cells. These findings shed new light on the pathogenesis of liver pathology in murine schistosomiasis.[Figure not available: see fulltext.]