A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice
A dichotomous role for nitric oxide during acute Toxoplasma gondii infection in mice
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DOI：
10.1073/pnas.94.25.13955
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发表时间：
1997-12-09
影响因子：
11.1
通讯作者：
Kasper, LH
中科院分区：
文献类型：
--
作者：
Khan, IA;Schwartzman, JD;Kasper, LH
巨噬细胞产生的一氧化氮被认为是一种重要的杀微生物机制，用于多种细胞内病原体，包括弓形虫。诱导型一氧化氮合酶基因（iNOS）靶向破坏的小鼠经口感染T。弓形虫组织囊肿与父母对照相比，死亡时间延长。对感染小鼠组织的组织学分析显示，INOS-/-小鼠的各种组织中存在散在的寄生虫炎症小病灶，而亲代C57 BL/6小鼠的组织具有更广泛的组织炎症，几乎没有可见的寄生虫。特别是，广泛的溃疡和坏死的远端小肠和脂肪变性的肝脏被认为是在感染后第7天的亲代小鼠，与iNOS-/-小鼠相比，这些组织出现正常。血清干扰素γ和肿瘤坏死因子α水平感染后同样升高两种小鼠品系。用一氧化氮合酶抑制剂氨基胍治疗亲代小鼠，可防止这些小鼠的早期死亡以及在急性感染的对照亲代小鼠中观察到的肝变性和小肠坏死。提示急性感染T.弓形虫可以杀死细胞内的寄生虫，但对宿主是有害的，甚至是致命的。
Production of nitric oxide by macrophages is believed to be an important microbicidal mechanism for a variety of intracellular pathogens, including Toxoplasma gondii. Mice with a targeted disruption of the inducible nitric oxide synthase gene (iNOS) were infected orally with T. gondii tissue cysts. Time to death was prolonged compared with parental controls. Histologic analysis of tissue from infected mice showed scattered small foci of inflammation with parasites in various tissues of INOS-/-mice, whereas tissue from the parental C57BL/6 mice had more extensive tissue inflammation with few visible parasites. In particular, extensive ulceration and necrosis of distal small intestine and fatty degeneration of the liver was seen in the parental mice at day 7 postinfection, as compared with the iNOS-/-mice where these tissues appeared normal. Serum interferon gamma and tumor necrosis factor alpha levels postinfection were equally elevated in both mouse strains. Treatment of the parental mice with a NO synthase inhibitor, aminoguanidine, prevented early death in these mice as well as the hepatic degeneration and small bowel necrosis seen in acutely infected control parentals. These findings indicate that NO production during acute infection with T. gondii can kill intracellular parasites but can be detrimental, even lethal, to the host.