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, γδ T 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) δ knockout (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 γδ T cells and secreted IL-17A. Compared with the WT mice, TCR δ deficiency resulted in reduced pathological impairment and fibrosis in the liver and increased survival in infected mice. In addition, the profibrogenic effects of γδ T 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, γδ T 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.