Bifidobacterium infantis regulates the programmed cell death 1 pathway and immune response in mice with inflammatory bowel disease

摘要

BACKGROUND Inflammatory bowel disease(IBD)is caused by an abnormal immune response.Programmed cell death 1(PD-1)is an immunostimulatory molecule,which interacts with PD ligand(PD-L1)playing a prime important role among autoimmune diseases.Bifidobacterium infantis(B.infantis)can promote the differentiation of CD(cluster of differentiation)4^(+)T cells into regulatory T cells(Tregs).Tregs participate in the development of IBD and may be related to disease activity.B.infantis amplify the expression level of PD-1,PD-L1 and Tregs’nuclear transcription factor forkhead box protein 3(Foxp3).But the mechanism of B.infantis on PD-1/PD-L1 signaling remains unclear.AIM To explore the mechanism of B.infantis regulating the immune response in IBD.METHODS Forty-eight-week-old BALB/c mice were randomly divided into five groups:The control group,dextran sulphate sodium(DSS)model group,DSS+B.infantis group,DSS+B.infantis+anti-PD-L1 group,and DSS+anti-PD-L1 group.The control group mice were given drinking water freely,the other four groups were given drinking water containing 5%DSS freely.The control group,DSS model group,and DSS+anti-PD-L1 group were given normal saline(NS)400μL daily by gastric lavage,and the DSS+B.infantis group and DSS+B.infantis+anti-PDL1 group were given NS and 1×109 colony-forming unit of B.infantis daily by gastric lavage.The DSS+B.infantis+anti-PD-L1 group and DSS+anti-PD-L1 group were given 200μg of PD-L1 blocker intraperitoneally at days 0,3,5,and 7;the control group,DSS+anti-PD-L1 group,and DSS+B.infantis group were given an intraperitoneal injection of an equal volume of phosphate buffered saline(PBS).Changes in PD-L1,PD-1,Foxp3,interleukin(IL)-10,and transforming growth factorβ(TGF-β)1 protein and gene expression were observed.Flow cytometry was used to observe changes in CD4^(+),CD25^(+),Foxp3^(+)cell numbers in the blood and spleen.RESULTS Compared to the control group,the expression of PD-1,Foxp3,IL-10,and TGF-β1 was significantly decreased in the intestinal tract of the DSS mice(P<0.05).Compared to the control group,the proportion of CD4^(+),CD25^(+),Foxp3^(+)cells in spleen and blood of DSS group was visibly katabatic(P<0.05).B.infantis upgraded the express of PD-L1,PD-1,Foxp3,IL-10,and TGF-β1(P<0.05)and increased the proportion of CD4^(+),CD25^(+),Foxp3^(+)cells both in spleen and blood(P<0.05).After blocking PD-L1,the increase in Foxp3,IL-10,and TGF-β1 protein and gene by B.infantis was inhibited(P<0.05),and the proliferation of CD4^(+),CD25^(+),Foxp3^(+)cells in the spleen and blood was also inhibited(P<0.05).After blocking PD-L1,the messenger ribonucleic acid and protein expression of PD-1 were invariant.CONCLUSION It is potential that B.infantis boost the proliferation of CD4^(+),CD25^(+),Foxp3^(+)T cells in both spleen and blood,as well as the expression of Foxp3 in the intestinal tract by activating the PD-1/PD-L1 pathway.