Changes of pulmonary co-signaling molecules in influenza A(H1N1)virus infected mice
Background Influenza A virus is highly infectious with a high mortality rate in severe infection cases.Co-signaling molecules are important molecules involved in immune response.Exploring the changing characteristics and correlation between pulmonary viral load and co-signaling molecules after influenza infection can provide reference for the treatment of influenza A virus infection.Objective To explore the changing characteristics of pulmonary viral load and its association with co-signaling molecules mRNA expression in mice infected with influenza A virus A/Puerto Rico/8/34(H1N1)(PR8 strain).Methods Totally 72 BALB/c mice aged 7 weeks were randomly divided into high dose virus group(108TCID50/mL,50 μL/mouse,n=32),low dose virus group(104TCID50/mL,50uL/mouse,n=32)and control group(PBS,50uL/mouse,n=8),8,8 and 2 mice were sacrificed in the three groups at each time point of 24 h,48 h,72 h and 96 h after infection,respectively.All mice were dissected for the left lung which used for HE staining,qRT-PCR was applied to detect the pulmonary virus load and the relative mRNA expression levels of co-signaling molecules CD28,CD226,ICOS,CTLA-4,TIGIT and PD-1.The correlation between pulmonary viral load and mRNA expression of co-signaling molecules were analyzed in all mice infected with high and low dose viruses.Results Within 96 h after infection,the lung injury of high dose virus group was more severe than that of low dose virus group,and the mRNA expression of co-stimulatory molecules CD28,CD226 and ICOS was decreased(all P＜0.05).In the high dose virus group,the relative expression of PD-1 mRNA increased at 24 h after infection(P＜0.01),the relative expression of CTLA-4 mRNA increased(P＜0.01)and the viral replication reached to the peak at 48 h after infection.In the low dose virus group,the relative expression of PD-1 mRNA increased(P＜0.05)and the viral replication reached to the peak at 72 h after infection,the relative expression of CTLA-4 mRNA increased(P＜0.01)at 96 h after infection.The pulmonary viral load of infected mice was positively correlated with the relative expression level of PD-1 mRNA(r=0.54,P＜0.001),and negatively correlated with the relative expression level of CD226 mRNA(r=-0.34,P=0.006).Conclusion After infected with influenza A virus,the early appearance of the increased mRNA expression of CTLA-4 and PD-1 may indicate severe infection.PD-1 and CD226 in mice lung tissue may be the co-signaling molecular targets correlated with pulmonary viral load.
influenza A virusviral pneumoniaco-signaling moleculesco-stimulatory moleculesco-inhibitory molecules
万方数据
维普
