首页> 外文期刊>Infection and immunity >Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain
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Long-Term Immunity to Lethal Acute or Chronic Type II Toxoplasma gondii Infection Is Effectively Induced in Genetically Susceptible C57BL/6 Mice by Immunization with an Attenuated Type I Vaccine Strain

机译:通过减毒的I型疫苗株免疫可遗传易感的C57BL / 6小鼠有效诱导致死性急性或慢性II型弓形虫感染的长期免疫。

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C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized B6 mice chronically infected with ME49 survived for at least 12 months without succumbing to the chronic infection. Potent immunity to type II challenge infections persisted for at least 10 months after vaccination. While the cps1-1 strain-elicited immunity did not prevent the establishment of a chronic infection or clear established brain cysts, cps1-1 strain-elicited CD8+ immune T cells significantly inhibited recrudescence of brain cysts during chronic ME49 infection. In addition, we show that uracil starvation of the cps1-1 strain induces early markers of bradyzoite differentiation. Collectively, these results suggest that more effective immune control of chronic type II infection in the genetically susceptible B6 background is established by vaccination with the nonreplicating type I uracil auxotroph cps1-1 strain.
机译:C57BL / 6(B6)小鼠在基因上高度易受慢性II型弓形虫的感染,而这种感染总是会导致致命的弓形体脑炎。我们研究了减毒的I型疫苗株在易感B6小鼠中引起对致命的急性或慢性II型感染的长期免疫的能力。用I型 cps1-1 疫苗株免疫的小鼠不易受II型株ME49的致死性(100个囊肿)攻击。与未经攻击的小鼠相比,用10个ME49囊肿攻击的免疫小鼠与未处理的小鼠相比,脑囊肿和寄生虫负担显着降低。值得注意的是,长期感染ME49的 cps1-1 株免疫B6小鼠存活了至少12个月,没有屈服于慢性感染。接种疫苗后,对II型挑战感染的有效免疫力至少持续了10个月。虽然 cps1-1 菌株引起的免疫不能阻止慢性感染的建立或清除已建立的脑囊肿,但是 cps1-1 菌株引起的CD8 + <在慢性ME49感染期间,免疫T细胞显着抑制脑囊肿的复发。此外,我们显示 cps1-1 菌株的尿嘧啶饥饿诱导了缓殖子分化的早期标记。总体而言,这些结果表明,通过对非复制性I型尿嘧啶营养缺陷型 cps1-1 株进行疫苗接种,可以建立在遗传易感性B6背景下对慢性II型感染更有效的免疫控制。

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