摘要
目的探讨程序性死亡分子1(programmed death-1,PD-1)对旋毛虫感染小鼠肌组织中细胞浸润及免疫反应类型的影响。方法以旋毛虫肌幼虫(400条/只)分别感染C57BL/6J遗传背景野生型(wild type,WT)小鼠和PD-1基因缺失(PD-1 deficient,PD-1^(-/-))小鼠,于感染第35天取材。免疫组化检测肌组织中幼虫囊包周围炎性细胞及成纤维细胞比例;ELISA检测肌组织中细胞因子干扰素γ(interferon-γ,INF-γ)、白细胞介素(interleukin,IL)-4、IL-5、IL-13、嗜酸性粒细胞趋化因子(eotaxin)表达水平;在感染后不同时间点取外周血,流式细胞术检测小鼠外周血及脾淋巴细胞CD4^(+)IFN-γ^(+)Th1、CD4^(+)IL-4^(+)Th2比例。结果旋毛虫感染后,PD-1^(-/-)小鼠肌组织幼虫囊包周围嗜酸性粒细胞(eosinophils,Eos)、成纤维细胞占浸润总细胞数的比例显著低于WT小鼠(P<0.01),而巨噬细胞、T细胞和B细胞占浸润总细胞数的比例高于WT小鼠(P<0.01);PD-1^(-/-)小鼠肌组织中细胞因子IL-4、IL-5、IL-13、eotaxin的水平显著低于WT小鼠(P<0.05),而细胞因子IFN-γ表达水平与WT型小鼠无统计学差异;PD-1^(-/-)小鼠外周血及脾CD4^(+)T细胞中Th2细胞的比例显著低于WT小鼠,而Th1细胞的比例与WT小鼠没有明显差异。结论PD-1缺失可导致感染小鼠嗜酸性粒细胞关键趋化因子及成纤维细胞形成的关键细胞因子表达下降,及肌组织中相应细胞浸润减少,而该作用可能与PD-1缺失所致的Th2型免疫反应下降有关。
Objective To investigate the effect of programmed death-1(PD-1)on cell infiltration in muscle tissue and immune response types in mice infected with Trichinella spiralis.Methods C57BL/6J wild-type(WT)and PD-1 deficient(PD-1^(-/-))mice were infected with T.spiralis(400 muscle larvae per mouse),and samples were collected on day 35 after infection.The proportions of infiltrating inflammatory cells and fibroblasts around encapsulated larvae were assessed by immunohistochemistry.The expression levels of interferon-γ(IFN-γ),interleukin(IL)-4,IL-5,IL-13,and eotaxin in muscle tissue were measured using enzyme-linked immunosorbent assay.Peripheral blood and spleen were collected at different time points after infection.The percentages of CD4^(+)IFN-γ^(+)Th1 and CD4^(+)IL-4^(+)Th2 within CD4^(+)T cells population in peripheral blood and spleen of mice were analyzed using flow cytometry.Results The proportions of eosinophils and fibroblasts among total infiltrating cells around the encapsulated larvae in the muscle of PD-1^(-/-)mice were significantly lower than those in WT mice after T.spiralis infection(P<0.01).The infected PD-1^(-/-)mice exhibited higher proportions of macrophages,T cells and B cells in total infiltrating cells than the infected WT mice(P<0.01).The levels of IL-4,IL-5,IL-13,and eotaxin in the muscle tissue of infected PD-1^(-/-)mice were significantly lower than those in infected WT mice(P<0.05).However,IFN-γlevels were not significantly different between the infected WT and PD-1^(-/-)mice.The proportions of Th2 cells in CD4^(+)T cells from peripheral blood and spleen of infected PD-1^(-/-)mice were significantly lower than those in infected WT mice,whereas the proportion of Th1 cells showed no difference among the infected groups.Conclusions PD-1 deletion results in decreased expression of key chemokines of eosinophils and key cytokines of fibroblast formation,and a corresponding decrease in inflammatory cells in muscle in T.spiralis-infected mice.This effect may be associated with a diminished Th2 immune response caused by PD-1 deletion.
作者
赵思蒙
黄欣扬
刘祎琪
张瑶
于艳
黄京京
诸欣平
程喻力
ZHAO Si-meng;HUANG Xin-yang;LIU Yi-qi;ZHANG Yao;YU Yan;HUANG Jing-jing;ZHU Xin-ping;CHENG Yu-li(Department of Parasitology,School of Basic Medical Science,Capital Medical University,Beijing 100069,China)
出处
《寄生虫与医学昆虫学报》
2025年第2期65-72,共8页
Acta Parasitologica et Medica Entomologica Sinica
基金
北京市自然科学基金项目(7202008)
国家自然科学基金项目(No.81572016)。
