Peroxiredoxin 3 promotes IL-12 production from macrophages and partially protects mice against infection with Toxoplasma gondii
Peroxiredoxin 3 promotes IL-12 production from macrophages and partially protects mice against infection with Toxoplasma gondii
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DOI：
10.1016/j.parint.2016.09.008
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发表时间：
2016-12-01
影响因子：
1.9
通讯作者：
Nishikawa, Yoshifumi
中科院分区：
文献类型：
--
作者：
Fereig, Ragab M.;Nishikawa, Yoshifumi
弓形虫病仍然是全世界人类和各种家畜和野生动物的一种危及生命的感染。它是由细胞内原生动物寄生虫刚地弓形虫引起的。过氧化物还毒素（Prxs）是一个抗氧化酶家族，保护细胞免受氢过氧化物的氧化应激。近年来，一些研究报道了弓形虫衍生酶在触发针对弓形虫感染的保护性免疫中的潜在用途。因此，本研究旨在探讨TgPrx3的免疫原性和保护作用。用融合谷胱甘肽-s转移酶（TgPrx3- gst）的重组TgPrx3蛋白体外刺激腹腔巨噬细胞可增强IL-12p40的产生，表明TgPrx3具有免疫刺激潜力。接下来，通过皮下接种TgPrx3-GST (25 pmol)，以重组GST或PBS为对照，研究其保护效果。用TgPrx3-GST免疫的小鼠在IgG1和IgG2c同型中表现出特异性抗体的显著升高。此外，用相同抗原免疫小鼠的tgprx3 - gst致敏细胞中，干扰素γ的产生和脾脏细胞的增殖显著增加。在免疫tgprx3 - gst的小鼠中，弓形虫感染的严重程度趋于减轻，这可以从它们更高的存活率和更低的大脑寄生虫负荷中得到证明。总之，TgPrx3免疫诱导了特异性的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。我们的结果提示TgPrx3可能被用作抗弓形虫感染的候选疫苗。2016爱思唯尔爱尔兰有限公司版权所有。
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 (25 pmol), 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. (C) 2016 Elsevier Ireland Ltd. All rights reserved.