PD-1在旋毛虫感染所致小鼠小肠与骨骼肌组织病理学改变中的作用

EFFECTS OF PD-1 ON HISTOPATHOLOGICAL CHANGES OF INTESTINAL AND SKELETAL MUSCLES IN MICE INFECTED WITH TRICHINELLA SPIRALIS

为探讨程序性死亡分子1(programmed death-1,PD-1)对旋毛虫感染小鼠组织病理学改变的影响,以旋毛虫肌幼虫(400条/只)分别感染C57BL/6遗传背景野生(WT)小鼠和PD-1基因缺失(PD-1^(-/-),KO)小鼠。于感染后第6 d取小鼠肠组织,第28、42、60 d取膈肌组织切片,HE染色观察组织病理学变化;感染后第60 d取膈肌组织Masson染色观察囊包周围肌组织纤维化水平。HE染色结果显示,感染后第6 d WT小鼠和PD-1^(-/-)小鼠肠组织肠绒毛长度/隐窝的长度(V/C)的比值和炎症细胞浸润数量均无显著差异(P>0.05);在感染后第28、42和60 d,PD-1^(-/-)小鼠肌组织中单位视野幼虫囊包数和炎症细胞浸润数量在各时间点均显著高于WT小鼠,且随感染时间延长,两组小鼠肌组织中炎症细胞数量均呈下降趋势。Masson染色结果显示,感染第60 d WT小鼠单个囊包周围组织纤维化面积明显高于PD-1^(-/-)小鼠。上述结果表明,PD-1对旋毛虫感染肠型期肠组织免疫病理反应无显著影响,但对肌型期幼虫在肌肉的寄生以及肌组织炎症反应具有抑制作用,并对修复期幼虫囊包周围组织纤维化具有促进作用。本研究为阐明PD-1在旋毛虫感染所致宿主组织病理损伤中的调节作用提供了实验证据。

The purpose of present paper is to investigate the effect of programmed death-1(PD-1)on the histopathological changes of mice infected with Trichinella spiralis.The 400 T.spiralis muscle larvae(each)were employed to infect the C57BL/6 genetic background wild mice(WT)and PD-1 gene deficient mice(PD-1^(-/-),KO).The intestinal tissues of mice were collected 6 days post infection(dpi),and the diaphragmatic tissue were collected at 28^(th),42^(nd) and 60^(th) dpi to observe the histopathological changes by HE staining.The level of fibrosis of diaphragmatic tissue was measured by Masson staining at 60^(th) dpi.The results of HE staining showed no significant difference in the villus length/crypt length(V/C)and number of inflammatory cells in the intestinal tissue between the WT mice and PD-1^(-/-)mice at 6 dpi(P>0.05).On the 28^(th),42^(nd) and 60^(th) dpi,the number of larval cyst and infiltration of inflammatory cells per unit field of vision in the mouse muscle tissue were significantly higher in PD-1^(-/-)mice than in WT mice at each time point(P<0.01),and,along with the extension of the infection time,the number of inflammatory cells in the muscle tissues showed a downward trend in the both groups.Masson staining showed that the fibrotic area of tissue around single capsule was significantly higher in WT mice than in PD-1^(-/-)mice at 60 th dpi(P<0.05).The results mentioned about suggested that PD-1 has no obvious effect on the intestinal immunopathology at the enterotype stage of T.spiralis infection,but may inhibit the survive of larva in the muscle and its inflammatory reaction at the muscle stage,and promoted the fibrosis of the tissue around the larval cyst at the repair stage.The present study has provided the experimental evidence to elucidate the regulatory role of PD-1 in host histocytopathic injury induced by T.spiralis infection.