Fereig Ragab M, Nishikawa Yoshifumi
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.
National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Inada-cho, Obihiro, Hokkaido 080-8555, Japan.
Parasitol Int. 2016 Dec;65(6 Pt A):741-748. doi: 10.1016/j.parint.2016.09.008. Epub 2016 Sep 16.
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.
弓形虫病仍然是一种威胁全球人类以及各种家畜和野生动物生命的感染性疾病。它由专性细胞内原生动物寄生虫刚地弓形虫引起。过氧化物还原酶（Prxs）是一类抗氧化酶家族，可保护细胞免受氢过氧化物的氧化应激。近年来，多项研究报道了刚地弓形虫衍生酶在引发针对刚地弓形虫感染的保护性免疫方面的潜在用途。因此，本研究旨在调查TgPrx3的免疫原性和保护效力。用与谷胱甘肽-S转移酶融合的重组TgPrx3蛋白（TgPrx3-GST）体外刺激腹膜巨噬细胞可增强IL-12p40的产生，表明TgPrx3具有免疫刺激潜力。接下来，通过给小鼠皮下接种TgPrx3-GST（25pmol）来研究保护效力，并用重组GST或PBS作为对照。用TgPrx3-GST免疫的小鼠在IgG1和IgG2c同种型方面表现出特异性抗体的显著升高。此外，在用相同抗原免疫的小鼠的TgPrx3-GST致敏细胞中，干扰素-γ的产生和脾细胞增殖显著增加。在TgPrx3-GST免疫的小鼠中，刚地弓形虫感染的严重程度趋于减轻，这表现为它们较高的存活率和较低的脑内寄生虫负荷。总之，TgPrx3免疫诱导了特异性体液和细胞免疫反应，并部分保护小鼠免受致命的弓形虫病感染。我们的结果表明TgPrx3可能作为抗刚地弓形虫感染的候选疫苗。
