Zhen Tang, Tingyu Zhou, Wanping Luo, Mingyi Shui, Jiaxuan Zhang, Cuiping Liu, Xiaoting Wang
Schistosoma japonicum infection causes egg-induced hepatic granulomatous inflammation together with extensive remodelling of host immunity. Although infection is known to progress from early Th1-associated immunity to egg-driven type 2 responses, the temporal relationships among egg-induced pathology, CD4+ T-cell polarization, T follicular helper (Tfh)-like phenotypes and parasite-specific humoral immunity remain incompletely defined. We therefore infected BALB/c mice with S. japonicum and examined them at serial time points after infection, assessing hepatic histopathology, serum ALT and AST activities, T-cell frequencies, cytokine-producing CD4+ T cells, helper-lineage transcription factors, PD-1 and ICOS expression on T cells, PD-L1 and ICOSL expression on B cells, CXCR5+ICOS+ phenotypic Tfh-like cells and serum SEA-specific IgG, with five biologically independent mice at each time point. Egg-associated hepatic granulomas first became apparent at week 5, enlarged during the middle stage of infection and regressed at later time points. Early infection was characterized by increased IFN-γ-producing CD4+ T cells and elevated Tbx21 expression; following egg deposition, IL-4-, IL-17A- and IL-21-producing CD4+ T cells and Gata3, Rorc and Bcl6 expression increased, and PD-1 and ICOS on CD4+ T cells together with PD-L1 and ICOSL on B cells changed dynamically over the course of infection. By week 8, CXCR5+ICOS+ Tfh-like cells were increased in the spleen, mesenteric lymph nodes and peripheral blood, and SEA-specific IgG had risen markedly after egg deposition and correlated positively with the frequency of splenic CXCR5+ICOS+ CD4+ T cells (rs = 0.3979, p < 0.001). Egg deposition thus represents a temporal immunological transition point in S. japonicum infection: the onset of egg-induced hepatic pathology coincides with the shift from early Th1-associated features to Th2-, Th17-, Tfh-like and SEA-specific humoral responses.