CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES >
Preliminary study on the changes of plymorphonucler myeloid-derived suppressor cells in the spleen of mice infected with Schistosoma japonicum
Received date: 2021-12-20
Revised date: 2022-03-20
Online published: 2022-07-06
Supported by
Shanghai Health and Family Planning Commission Project for Youth(20214Y0206);Natural Science Foundation of Shanghai(19ZR1462600);the Surface Project of National Natural Science Foundation of China(81971969);the Surface Project of National Natural Science Foundation of China(81772225)
Objective To explore the dynamic changes of the proportion, function and spleen histopathology of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) in the spleen of mice infected with Schistosoma japonicum. Methods Thirty-six BALB/c mice aged 6-8 weeks were randomly assigned into the infected group and control group, with 18 mice in each group. Mice in the infection group were infected with S. japonicum cercariae (20 ± 1)/mouse. At 4, 6 and 8 weeks post-infection, the spleen from 6 mice, which were randomly selected from each group, were collected, followed by calculating the spleen coefficients after weighting. The spleen tissues were fixed, sliced and stained with hematoxylin-eosin (HE) to observe the pathological changes microscopically. Spleen single cell suspension was prepared for examining the dynamic changes of PMN-MDSCs proportion in splenic lymphocytes by flow cytometry. Fluorescent quantitative PCR was used to determine the mRNA relative expression expression level of PMN-MDSC related inflammation factors, including interleukin-6 (IL-6), S100 calcium binding protein A8 (S100A8）, S100A9, and the cell function factor arginase 1 (Arg1), nitric oxide synthase (iNOS), heme-binding membrane glycoprotein 91(gp91), transforming growth factor-β(TGF-β), and IL-10 in the spleen tissues. Results At 4, 6 and 8 weeks after infection, the spleen weight and spleen coefficient in infection group were(179 ± 10.19)mg, (350.3 ± 16.84)mg, (414.3 ± 18.98)mg, and (0.93 ± 0.03)%, (1.97 ± 0.10)%, (2.31 ± 0.08)%, respectively, which were all significantly higher than that in the control group[(108.2 ± 9.93)mg and (0.51 ± 0.04)%] (F = 101.3, 143.7, P < 0.01). HE staining showed that at 4-6 weeks after infection, the inflammatory cell band gradually increased, while the lymphoid follicles of the spleen decreased, and the germinal center decreased or even disappeared compared with the control group. At 6-8 weeks after infection, the inflammatory cell band decreased gradually, and the lymphoid follicles and germinal centre structure of the spleen proliferated gradually compared with the control group. Splenic PMN-MDSCs proportion in infection group were (1.53 ± 0.16)%, (28.40 ± 2.35)%, (38.67 ± 1.94)%, which were all significantly higher than that in the control group (0.80 ± 0.10)% (F = 326.5, P < 0.01). Real-time quantitative PCR showed that at 6 weeks post-infection, the relative level of mRNA expression of IL-6, S100A8, S100A9, gp91, Arg1, iNOS, IL-10 and TGF-β in splenic tissue were 2.74 ± 0.25, 51.4 ± 1.25, 39.20 ± 2.83, 2.15 ± 0.08, 2.33 ± 0.39, 1.57 ± 0.08, 2.20 ± 0.39 and 1.44 ± 0.05, respectively, which were all significantly higher than that in the control group [1.05 ± 0.10, 1.01 ± 0.11, 1.02 ± 0.07, 1.04 ± 0.09, 1.01 ± 0.06, 1.00 ± 0.05, 0.98 ± 0.20 and 1.00 ± 0.04(t = 6.367, 40.07, 13.50, 9.311, 3.315, 5.642, 2.764, 6.914, P < 0.05, P < 0.01)]. The relative iNOS mRNA expression in splenic PMN-MDSCs was higher than that in the control group (t = 0.6134, P < 0.01) and the relative of IL-10 mRNA expression level was no statistically significantly different between the infection group and the control group(t = 1.176, P > 0.05). At 8 weeks after infection, the relative IL-6, S100A8, S100A9, Arg1, iNOS and IL-10 mRNA expression levels in splenic tissue were all significantly higher than those in the control group (t = 2.496, 5.145, 9.518, 3.938, 4.819, 2.251, P < 0.05, P < 0.01). In the splenic of PMN-MDSCs, the relative iNOS mRNA expression level and IL-10 were 32.12 ± 2.30, and 2.64 ± 0.37, respectively, which were higher than that at 4 weeks after infection (1.08 ± 0.01, 1.14 ± 0.35), and also higher than that at 6 weeks after infection (12.06 ± 1.80, 1.50 ± 0.36), as well as the control group (1.02 ± 0.13, 1.06 ± 0.12) (F = 100.6, 5.471, P < 0.01). Conclusion At 4~6 weeks post S. japonicum infection, the spleen tissue presented strong inflammatory response, at 6~8 weeks after infection, the secretion of the inhibitory factor IL-10 of PMN-MDSC was significantly increased, and the spleen tissue structure was gradually proliferated.
Key words： S. japonicum; PMN-MDSC; Spleen; Cytokine; Inflammation
ZHANG Xiao-cheng , GAO Yuan , HU Yuan , CAO Jian-ping . Preliminary study on the changes of plymorphonucler myeloid-derived suppressor cells in the spleen of mice infected with Schistosoma japonicum[J]. CHINESE JOURNAL OF PARASITOLOGY AND PARASITIC DISEASES, 2022 , 40(3) : 330 -336 . DOI: 10.12140/j.issn.1000-7423.2022.03.008
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