Modulation Of Gene Expression In Liver And Peripheral Blood Lymphocytes,and Cytokines In Serum Of Buffaloes By Fasciola Gigantica Infection

Fasciolasis,caused by Fasciola gigantica and Fasciola hepatica,is an important zoonosis.Fasciola infection causes significant economic losses to livestock farming including buffalo,cattle and sheep.Fasciola infection leads to a serious public health problem due to its infection in humans,thus studies of immune responses of the natural hosts like buffalos and the immunomodulation caused by F.gigantica have important implications for controlling fasciolasis.We characterized the transcriptome of infected buffalo livers,the innate immune-related genes levels of liver and PBL,and levels of ten cytokines of infected buffalo serum for the first time.Our results demonstrated the interactions between F.gigantica and buffaloes in genetic and immunological level.Fasciola gigantica infection induced influences on immune responses in hosts and persistent immunomodulation during infection.These findings will lay the foundation for further studying regulatory mechanisms F.gigantica.The details are as follows:1.Transcriptomic analyses of buffalo liver infected by F.gigantica revealed that immune-related immune components were regulated in infected liver at 3 days post infection(DPI),42 DPI and 70 DPI.In early infection,MHC-Ⅱ signal pathway was significant downregulated which remind that F.gigantica modulated immune-related genes to establish infection and survive in hosts.Meantime,F.gigantica facilitates its survival within hosts by downregulating the expression of lipopolysaccharide binding protein(LBP)then affect pro-inflammation cytokines expression.In addition,some biological processes such as metabolism,bile secretion were changed during infection.2.Fluorescent quantitation PCR was used to examine mRNA level of liver and peripheral blood lymphocytes(PBL)of buffaloes infected with F.gigantica at 3 DPI,10 DPI,28 DPI and 70 DPI.TLR4,TRIF,NF-κB,NLRP3 inflammasome,cell polarization and NOD1 signal pathway were changed during infection.We summarized that F.gigantica carried out immunomodulation to escape immune recognition and elimination for survival.3.Ten cytokines(IL-17,IL-1β,IL-4,IL-13,IFN-γ,IL-2,IL-10,IL-12,IL-6,TGF-β)in buffalo serum challenged by F.gigantica were examined by enzyme linked immunosorbent assay(ELISA).Our work revealed a polarized Th2 immune response during early infection as indicated by the slightly high levels of IL-4,IL-10 and IL-13 cytokines,and the reduced levels of IFN-γ,Il-2,IL-6,IL-12,and IL-1β cytokines.Although a complex interplay among Th1,Th2,and Th17 appear to underlie the immune response elicited against F.gigantica,the present results suggest that modest Th2-type response in early infection is needed to downregulate harmful Th1-and Th17-type inflammatory responses.Our data also suggest a state of immune-suppression during the late phase of the infection.These findings support continued investigation into immune response mechanisms enabling F.gigantica to evade,interfere and suppress host-immune defences.