[Effects of glycolytic pathway on generation of regulatory T cells during Schistosoma japonicum infection].

OBJECTIVE: To assess the influence of glycolytic pathway on the proportion and numbers of regulatory T cells during Schistosoma japonicum infection. METHODS: A S. japonicum -infected mouse model was established, and C57/BL6 male mice infected with S. japonicum were subjected to intraperitoneal injections of with the glycolytic inhibitor 2-Deoxy-D-glucose (2DG) or PBS for 6 times, and then the cells from spleen or mesenteric lymph nodes (LNs) were isolated and analyzed by flow cytometry (FCM) to detect the percentage of Glut1+CD4+ T cells and Treg cells. RESULTS: The proportions of Glut1+CD4+ T cells in the spleen (43.58%±2.50% vs. 21.15%±0.96%; t = 8.834, P < 0.01) and mesenteric LNs (38.97%±1.97% vs. 28.40%±2.11%; t = 3.662, P < 0.05) were higher in the normal mice than those in the infected mice, and the percentages of Treg cells in the spleen (6.83%±0.21% vs. 13.30%±0.35%; t = 15.65, P < 0.01) and LNs (8.26%±0.15% vs. 14.37%±0.44%; t = 13.14, P < 0.01) were lower in the normal mice than those in the infected mice. In addition, the proportions of Treg cells in the spleen (15.50%±0.76% vs. 13.07%±0.15%; t = 3.130, P < 0.05) and LNs (17.00% ±0.41% vs. 13.83%±0.18%; t = 6.947, P < 0.01) were higher in the infected mice injected intraperitoneally with 2DG than those in the infected mice injected intraperitoneally with PBS. CONCLUSIONS: Glycolytic pathway inhibits Treg differentiation in the spleen and mesenteric LNs of S. japonicum-infected mice.

[Study on role of TIGIT signal in Th1/Th2 balance in Schistosoma japonicum-infected mice].

OBJECTIVE: To investigate the role of TIGIT signal in Th1/Th2 balance in the process of Schistosoma japonicum infection. METHODS: Male C57BL/6 mice were infected with cercariae of S. japonicum, and normal uninfected mice served as the controls. The percentages of TIGIT+ cells, Ki67+CD3+CD4+TIGIT+ cells, Ki67+CD3+CD4+TIGIT- cells, IFN-γ+CD3+CD4+TIGIT+ cells, IFN-γ+CD3+CD4+TIGIT- cells, IL-4+CD3+CD4+TIGIT+ cells and IL-4+CD3+CD4+TIGIT- cells were evaluated in mouse spleen by flow cytometry. RESULTS: The proportion of TIGIT+CD4+ T cells was higher in the spleen of S. japonicum-infected mice than in the normal uninfected mice (29.30%±0.70% vs. 3.09%±0.50%; t = 8.834, P < 0.01) . However, no significant difference in the percentages of TIGIT+ CD8+ T cells between the infection group and normal controls (3.61%±0.26% vs. 3.58%±0.16%; t = 0.108, P > 0.05), and no significant difference was detected in the percentages of TIGIT+ cells in non-T cells between the infection group and controls (1.86%±0.19% vs.1.37%±0.17%; t = 1.931, P > 0.05) . In addition, the proportion of Ki67 in the TIGIT+ cells was higher than that in the TIGIT- cells (17.03%±0.64% vs. 6.59%±0.37%; t = 14.09, P < 0.01) . The Th2/Th1 ratio was higher in the TIGIT+CD4+ T cells than in the TIGIT-CD4+ T cells (39.28%±3.75% vs. 11.79%±1.64%; t = 6.721, P < 0.01) . CONCLUSIONS: The TIGIT signaling may be involved in the development of Th2 responses in the mice infected with S. japonicum.

[Schistosoma japonicum heat shock protein 60 enhances regulatory T cell immunosuppressive function by promoting the expressions of IL-10 and TGF-ß].

OBJECTIVE: To explore the possible mechanisms by which Schistosoma japonicum heat shock protein 60 (SjH-SP60) enhances CD4+CD25+ regulatory T cell (Treg) immunosuppressive function. METHODS: An in vitro method was used to investigate the effect of SjHSP60 on Treg immunosuppressive activity. Co-cultures in transwells and in vitro suppression assay were performed to investigate how SjHSP60 enhanced the immunosuppressive function of Tregs. Intracellular cytokine staining combined with flow cytometry was used to detect Treg-expressing IL-10 and TGF-ß, and flow cytometry was also used to analyze the expressions of Foxp3 and CTLA-4 in Tregs. RESULTS: SjHSP60 enhanced the immunosuppressive function of Tregs. Soluble cytokines IL-10 and TGF-ß mediated inhibitory activity of SjHSP60-triggered Tregs. SjHSP60 induced significant increases in both IL-10 and TGF-ß expressions of Tregs. Further investigation showed significant increased Foxp3 and CTLA-4 in SjHSP60-trggered Tregs. CONCLUSIONS: SjHSP60 enhances Treg immunosuppressive function by promoting the expressions of IL-10 and TGF-ß, possibly due to SjHSP60-mediated induction of Foxp3 and CTLA-4 in Tregs.

[Sex bias in generation and functional phenotypes of peripheral T follicular helper cells in schistosomiasis japonica].

OBJECTIVE: To study the influence of sex on the generation and function of T follicular helper (Tfh) cells in the process of Schistosoma japonicum infection. METHODS: Totally 50 schistosomiasis patients were selected in the endemic areas of Chizhou City, Anhui Province, and totally 50 healthy people were selected in the non-endemic areas of Chizhou City as the controls. The peripheral bloods were collected from the above study subjects, and the human peripheral blood mononuclear cells from male/female schistosomiasis japonica patients or healthy controls were collected into the sodium heparin tubes and purified by Ficoll-paque plus density gradient centrifugation. Then, the percentages of total Tfh cell, ICOS+ Tfh cells, and PD-1+ Tfh cells in the schistosomiasis male/female patients or healthy controls were evaluated by flow cytometry. RESULTS: Compared with the male and female healthy controls, the frequency of the total Tfh cells (Umale = 149.0, Ufemale = 39.5, both P < 0.01), the percentages of PD-1+ Tfh cells (tmale = 5.9, tfemale = 7.7, both P < 0.01) and ICOS+ Tfh cells (tmale = 3.2, tfemale = 5.9, both P < 0.01) of the male and female patients with schistosomiasis increased, all the differences were statistically significant. The further analysis showed that the percentage of total Tfh cells (U = 187.5, P < 0.05), ICOS+ Tfh cells (t = 3.2, P < 0.05), and PD-1+ Tfh cells (t = 3.0, P < 0.05) of the female patients were markedly higher than those of the male patients, all the differences were also statistically significant. CONCLUSIONS: Sex may be a crucial role in the generation and function of Tfh cells in the process of Schistosoma japonicum infection.