Khan I A, Matsuura T, Kasper L H
Department of Medicine, Dartmouth Medical School, Lebanon, NH 03756, USA.
J Immunol. 1998 Sep 15;161(6):2994-3000.
Induction of reactive nitrogen intermediates by IFN-gamma is presumed an important mechanism of host resistance against acute and chronic infection with Toxoplasma gondii. Although nitric oxide (NO) has been shown to be important in the control of parasite replication in vivo, the role of this molecule in vaccine-based immunity against T. gondii is unknown. Mice with a targeted disruption of inducible NO synthase (iNOS) were immunized with an avirulent temperature-sensitive strain of this parasite (ts-4). Both the parental C57BL/6 and the iNOS(-/-) mice survived infection with the ts-4 mutant. Oral challenge of the vaccinated mice with a lethal dose of cysts containing bradyzoites resulted in reduced parasite burden and increased survival compared with nonvaccinated control mice. Host immunity in the iNOS(-/-) mice, similar to that observed in the parental strain, appears dependent upon both IFN-gamma and CD8+ T cells. These findings suggest that although vaccine-based long-term immunity against T. gondii is dependent upon the induction of IFN-gamma, it does not rely upon the anti-microbial effect of NO.
γ干扰素诱导反应性氮中间产物被认为是宿主抵抗刚地弓形虫急性和慢性感染的重要机制。尽管一氧化氮（NO）已被证明在体内控制寄生虫复制方面很重要，但该分子在基于疫苗的抗弓形虫免疫中的作用尚不清楚。用这种寄生虫的无毒温度敏感株（ts-4）对诱导型一氧化氮合酶（iNOS）靶向破坏的小鼠进行免疫。亲代C57BL/6小鼠和iNOS（-/-）小鼠均在感染ts-4突变体后存活。与未接种疫苗的对照小鼠相比，用致死剂量的含有缓殖子的包囊对接种疫苗的小鼠进行口服攻击，导致寄生虫负荷降低，存活率提高。iNOS（-/-）小鼠的宿主免疫与亲代菌株中观察到的相似，似乎依赖于γ干扰素和CD8+T细胞。这些发现表明，尽管基于疫苗的针对弓形虫的长期免疫依赖于γ干扰素的诱导，但它并不依赖于NO的抗菌作用。
