Abstract
BackgroundCD4+ T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. However, the role of Tfh cells in schistosome infection is not fully understood. In this study, the dynamics and roles of Tfh cell regulation were examined. We demonstrated that granulocytic myeloid-derived suppressor cells (G-MDSC) can suppress the proliferation of Tfh cells.MethodsThe levels of Tfh cells and two other Th cells (Th1, Th2) were quantitated at different Schistosoma japonicum infection times (0,3, 5, 8, 13 weeks) using flow cytometry. The proliferation of Tfh cells stimulated by soluble egg antigen (SEA) and soluble worm antigen (SWA) in vivo and in vitro were analyzed. Tfh cells were co-cultured with MDSC to detect the proliferation of Tfh cells labelled by 5(6)-carboxyfluorescein diacetate N-succinimidyl ester. We dynamically monitored the expression of programmed cell death protein 1 (PD-1) on the surface of Tfh cells and programmed cell death ligand 1 (PD-L1) on the surface of MDSC at different infection times (0, 3, 5, 8 weeks). Naïve CD4+ T cells (in Tfh cell differentiation) were co-cultured with G-MDSC or monocytic MDSC in the presence, or in the absence, of PD-L1 blocking antibody.ResultsThe proportion of Tfh cells among CD4+ T cells increased gradually with time of S. japonicum infection, reaching a peak at 8 weeks, after which it decreased gradually. Both SEA and SWA caused an increase in Tfh cells in vitro and in vivo. It was found that MDSC can suppress the proliferation of Tfh cells. The expression of PD-1 on Tfh cells and PD-L1 from MDSC cells increased with prolongation of the infection cycle. G-MDSC might regulate Tfh cells through the PD-1/PD-L1 pathway.ConclusionsThe reported study not only reveals the dynamics of Tfh cell regulation during S. japonicum infection, but also provides evidence that G-MDSC may regulate Tfh cells by PD-1/PD-L1. This study provides strong evidence for the important role of Tfh cells in the immune response to S. japonicum infection.Graphical abstract
Highlights
CD4+ T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis
The reported study reveals the dynamics of T follicular helper (Tfh) cell regulation during S. japonicum infection, and provides evidence that G-myeloid-derived suppressor cells (MDSC) may regulate Tfh cells by Programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1)
This study provides strong evidence for the important role of Tfh cells in the immune response to S. japonicum infection
Summary
CD4+ T helper (Th) cells play critical roles in both host humoral and cellular immunity against parasitic infection and in the immunopathology of schistosomiasis. T follicular helper (Tfh) cells are a specialized subset of Th cells involved in immunity against infectious diseases. The mechanism of the host immune response to Schistosoma japonicum infection is complicated. Many immune cells are involved in the immune response to a S. japonicum infection, such as T helper type 1 (Th1), Th2, Th17, T follicular helper (Tfh), regulatory T (Treg) cells, dendritic cells (DCs) and myeloid-derived suppressor cells (MDSC). The inducible T-cell co-stimulator molecule on the Tfh cell surface can promote liver granuloma formation in mice infected with S. japonicum [6]. Research on Tfh cells and their involvement in the immune response to S. japonicum infection is limited and its findings unclear
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