Effects And Mechanism Of Different Antigens Of Echinococcus Granulosus On DC Mediated Immune Responses

Dendritic cells play important roles in parasite infections.Different antigens of parasite or different fragement of antigen of parasite have different effects on DC induced immune responses.Mice immunized with rEg.ferritin(recombinant ferritin of Echinococcus granulsous)and rEg10(recombinant antigen 10 of Echinococcus granulsous)produced widely divergent results against challenge of PSC of Echinococcus granulosus.To investigate mechanisms by which rEg.ferritin and rEg10 induced mice to produce different immune responses,changes in morphology and function of bone marrow DC stimulated by rEg.ferritin and rEg10 were examined.As we know Notch signal pathway is involved in the growth and differention of DC.The roles of Notch signal pathway in the immune responses of DC mediated antigens of Echinococcus granulosus were studied by examining the changes of the morphology and function of DCs after enhancing or inhibiting Notch signal pathway,and then these DCs was stimulated with rEg.ferritin and rEg10.DC stimulated with different antigens had different morphologies as observed by SEM(scan electron microscope)and TEM(transmission electron microsope).rEg10 or HF inhibited the maturation of DC and the expression of surface marker MHC?,CD80,CD86,and CD40,decreased the migration ability of DC,prevented T-cell proliferation,but enhanced the uptake abilities of DC.DC stimulated with rEg10 secreted a large amnount of IL-6,IL-10 and a low level of IL-12p70 and TNF-a.Additionally,in LPS plus rEg10 and HF group,LPS stimulated DC maturation,up-regulated the expression of surface markers and decresed the level of IL-6 and IL-10 and increased the level of TNF-?.Therefore,HF and rEg10 inhibited DC maturation,promoted DC to secrete cytokine of Th2,and induced Th2 immune response to protect parasite from being killed.On the contrary,rEg.ferritin and LPS stimulated DC maturation,up-regulated expression of surface markers of DC,and increased the migration ability.DC exposed in rEg.ferritin activated T-cell proliferation and produced higher level IL-12p70,TNF-?,IL-6 and IL-10,but rEg.ferritin plus LPS did not promote further maturation of DC.rEg.ferritin induced DC to produce cytokines of Th1 and Th2,and induced the immune response of Th1 and Th2.The effect of Notch signal pathway on DC was evalulated further.DAPT inhibited the development and maturation of bone marrow monocyte and impaired the abilities of DC.DC pre-treated with DAPT expressed lower level of the surface markers and had weaker migration ability when stimulated with rEg.ferritin.DAPT down regulated mRNA level of Notch 1,Hes 1,and Delta-4 of DC when exposed in rEgferritin and LPS.DC had no response or low response to antigen of rEg.ferritin and LPS,and the immune response induced by rEg.ferritin and LPS was blocked.Jagged 1 mediated the Notch signal pathway activation,promoted DC maturation and increased CD80 and CD86 expression in rEg10 group,and also up-regulated the mRNA level of Hes land Delta-4 in rEg10 group.Thess data suggest that Jagged 1 mediated Notch signal pathway may be involved in rEg10 induced immune response of Echinococcus granulosus infection,but may not be involved in rEg.ferritin induced immune response against Echinococcus granulosus infection.In summary Notch signal may play a role in Echnococcus granulosus infections through dependent or independent pathway.Strategy to activate or inhibit Notch signal pathway may has a potential for the prevention and cure of parasite diseases.