泡球蚴感染对小鼠肝脏TRIF/IRF3通路和IFITM3的影响OACSTPCD

Objective To explore the effects of alveolar hydatid cyst infection at different time points on TIR domain containing adaptor inducing interferon-β(TRIF)/interferon regulatory factor 3(IRF3)pathway and interferon-induced transmembrane protein 3(IFITM3)in mouse liver.Methods Liver tissues from patients with alveolar echinococcosis and other non-infectious liver diseases(hepatic hemangioma)were collected to observe the liver tissue pathological changes and the expression levels of IFITM3 and Forkhead box protein P3(Foxp3)by HE staining and immunohistochemical staining.Forty-eight female C57BL/6J mice were randomly divided into infection group(intraperitoneal infection with alveolar hydatid cysts for 8,30,60,90,180 d)and control group.Masson trichrome staining was used to observe the liver fibrotic changes in mice,and Western blot and real-time quantitative PCR were performed to detect the changes of TRIF/IRF3 pathway,IFITM3,and Foxp3 in mouse liver.Results Liver tissues of patients with alveolar echinococcosis showed a disordered arrangement of liver tissues around the lesions with large number of infiltrated inflammatory cell,while the liver tissues of patients with hepatic hemangioma remained intact.Immunohistochemical staining results showed the expression levels of IFITM3 and Foxp3 in patients with alveolar echinococcosis were increased compared to hepatic hemangioma patients.Masson trichrome staining revealed that alveolar hydatid cyst infection induced liver fibrotic changes in mice.Real-time quantitative PCR results showed that the expressions of TRIF,IRF3,IFNB1 and IFITM3 mRNA in mouse liver were higher at 60 d and 90 d in infection group than in control group(P＜0.05),and the expressions of TRIF,IFNB1 and IFITM3 mRNA showed no statistical difference at 180 d between two groups(P＞0.05).The expression of Foxp3 mRNA was increased,and then decreased,and increased again after alveolar hydatid cyst infection,and the expression of Foxp3 mRNA peaked at 180 d(P＜0.05).Western blot analysis demonstrated that the expressions of TRIF,IRFB1,and IFITM3 proteins were higher at 90 d in infection group than those in control group(P＜0.05),and there was no significant differences at 180 d between two groups(P＞0.05).At 90 d and 180 d,Foxp3 protein expression was higher in infection group than in control group,and peaked at 180 d(P＜0.05).Conclusion During the late infection with alveolar hydatid cyst,the TRIF/IRF3 pathway and IFITM3 expressions are downregulated in liver tissues,which affect the function of innate immunity in anti-pathogen,and suppress the anti-pathogen effect of host.