title: Peroxiredoxin 3 promotes IL-12 production from macrophages and partially protects mice against infection with Toxoplasma gondii.
abstract: Toxoplasmosis remains a life-threatening infection of humans and various domestic and wild animals worldwide. It is caused by the obligatory intracellular protozoan parasite Toxoplasma gondii. Peroxiredoxins (Prxs) are a family of antioxidant enzymes that protect cells from oxidative stress from hydroperoxides. In the recent years, several studies have reported the potential use of T. gondii-derived enzymes in triggering protective immunity against T. gondii infection. Therefore, this study was conducted to investigate the immunogenicity and protective efficacy of TgPrx3. In vitro stimulation of peritoneal macrophages with recombinant TgPrx3 protein fused to glutathione-S transferase (TgPrx3-GST) enhanced IL-12p40 production, indicating the immune-stimulating potentials of TgPrx3. Next, protective efficacy was investigated by subcutaneous inoculation of mice with TgPrx3-GST (25pmol), and recombinant GST or PBS were used as the controls. Mice immunized with TgPrx3-GST exhibited a significant elevation of specific antibodies in terms of IgG1 and IgG2c isotypes. Moreover, interferon-gamma production and spleen cell proliferation dramatically increased in the TgPrx3-GST-sensitized cells from mice immunized with the same antigen. The severity of the T. gondii infections tended to be attenuated in the TgPrx3-GST-immunized mice, as evidenced by their higher survival rates and lower parasite burdens in the brain. Altogether, TgPrx3 immunization induced specific humoral and cellular immune responses and partially protected the mice against lethal toxoplasmosis. Our results suggest the possible use of TgPrx3 as a vaccine candidate against T. gondii infections.
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan; Department of Animal Medicine, Faculty of Veterinary Medicine, South Valley University, Qena City, Qena 83523, Egypt.
authors.forename: Ragab M
authors.initials: RM
authors.lastname: Fereig
authors.affiliation: National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan. Electronic address: nisikawa@obihiro.ac.jp.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood* / Q000276:immunology; D000975:Antioxidants / Q000627:therapeutic use*; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics / Q000627:therapeutic use*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D053762:Interleukin-12 Subunit p40 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D059208:Parasite Load; D061105:Peroxiredoxin III / Q000235:genetics / Q000627:therapeutic use*; D016052:Protozoan Vaccines / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016415:Sequence Alignment; D013154:Spleen / Q000166:cytology; D014122:Toxoplasma / Q000187:drug effects* / Q000276:immunology; D014124:Toxoplasmosis, Animal / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control
chemical_list: D000913:Antibodies, Protozoan; D000975:Antioxidants; D007074:Immunoglobulin G; D053762:Interleukin-12 Subunit p40; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; D007371:Interferon-gamma; D061105:Peroxiredoxin III; D005982:Glutathione Transferase
keywords: Immunization; Peroxiredoxin 3; Toxoplasma gondii; Vaccine