ABSTRACT
The IPSE/alpha-1 gene (IL-4-inducing principle of Schistosoma mansoni eggs) is a major secreted glycoprotein of S. mansoni eggs that has a potent IL-4-inducing effect. To test the hypothesis that the immune evasion mechanism can be used to overcome the xenograft immune response, the IPSE/alpha-1 gene was transferred into pig fibroblasts, and the transgenic cells were transplanted into KM mice by subcutaneously injecting 10(5)cells per mouse. Cytokine levels were measured to examine the immune response polarization by real-time PCR and ELISA. Mice injected with pig fibroblasts containing a pIRES2-EGFP expression vector were used as a control group. In this group, both cellular and humoral immune responses were activated to reject the grafts alongside increases in all measured cytokine levels. In contrast, the experimental group injected with cells constitutively expressing the IPSE/alpha-1 gene demonstrated a significant decrease in Th1 response cytokines and a significant increase in Th2 response cytokines compared with the control group. These results imply that constitutive IPSE/alpha-1 expression can shift the Th1/Th2 balance of xenograft rejections toward the Th2 response while suppressing the Th1 response. In conclusion, IPSE/alpha-1 could influence the polarization of immune responses during xenograft rejection and suppress the Th1 response. Therefore, this parasitic immune evasion mechanism could be helpful in overcoming xenograft rejection.
Subject(s)
Egg Proteins/immunology , Helminth Proteins/immunology , Schistosoma mansoni/immunology , Th2 Cells/immunology , Animals , Antigens, Helminth/genetics , Cytokines/metabolism , Egg Proteins/genetics , Fibroblasts/immunology , Fibroblasts/transplantation , Genes, Helminth , Graft Rejection/immunology , Helminth Proteins/genetics , Host-Parasite Interactions/immunology , Mice , Schistosoma mansoni/genetics , Schistosoma mansoni/pathogenicity , Swine , Th1 Cells/immunology , Transfection , Transplantation, HeterologousABSTRACT
Infection with the intracellular protozoan parasite Toxoplasma gondii causes serious public health problems and is of great economic importance worldwide. The rhomboid proteins which are responsible for adhesion and invasion of host cells have been suggested as vaccine candidates against toxoplasmosis. A DNA vaccine (pVAX-ROM1) encoding T. gondii rhomboid protein 1 (TgROM1) gene was constructed and the immune response and protective efficacy of this vaccine against lethal challenge in BALB/c mice were evaluated. The results indicated that specific antibody and lymphocyte proliferative responses were elicited in mice receiving pVAX-ROM1. The production levels of IFN-γ, IL-2, IL-4, and IL-10, as well as the percentage of CD4(+) cells in mice vaccinated with pVAX-ROM1 were significantly increased respectively, compared to controls receiving either pVAX1 alone or PBS. After lethal challenge, the mice immunized with pVAX-ROM1 showed an increased survival time compared with the mice in the controls. Our data suggested that a DNA vaccine pVAX-ROM1 encoding T. gondii rhomboid protein 1 triggered strong humoral and cellular responses, and prolonged survival time against T. gondii infection in BALB/c mice.
Subject(s)
Protozoan Proteins/immunology , Protozoan Vaccines/immunology , Toxoplasma/immunology , Toxoplasmosis/immunology , Animals , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Cell Proliferation , Cytokines/genetics , Female , Gene Expression Regulation , HeLa Cells , Humans , Immunity, Humoral , Mice , Mice, Inbred BALB C , Random Allocation , Spleen/cytology , Survival Analysis , Toxoplasmosis/mortality , Toxoplasmosis/prevention & control , Vaccines, DNA/immunologyABSTRACT
Total nucleic acids from sporulated oocysts of Eimeria tenella isolated from Changchun in China were found to contain three extrachromosomal double-stranded RNA segments (dsRNAs) of 1.4, 2.4 and 3.6 kb in sizes. These RNAs were resistant to RNase A digestion under high salt concentration (0.3 M NaCl). RNA-dependent RNA polymerase (RDRP) activity was detected in crude extracts of E. tenella sporulated oocysts containing these nucleic acid species. Virus-like particles (VLPs) were shown to have a diameter of approximately 38 nm under Electron Microscopy (EM) after purification by sucrose density gradient centrifugation. In keeping with the nomenclature generally adopted for protozoan viruses, we have named this isolate as E. tenella virus (ETV) which is the first virus isolated from E. tenella.
