Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii.
Inducible nitric oxide is essential for host control of persistent but not acute infection with the intracellular pathogen Toxoplasma gondii.
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可诱导的一氧化氮对于对持续性的宿主控制，但不能用细胞内病原体弓形虫造成的急性感染。
DOI：
10.1084/jem.185.7.1261
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发表时间：
1997-04-07
影响因子：
15.3
通讯作者：
Sher, A
中科院分区：
文献类型：
--
作者：
Scharton-Kersten, T M;Yap, G;Magram, J;Sher, A
IFN-γ被反应性氮中间体的诱导是宿主对细胞内病原体的抗性的主要机制，以正式检验该假设，在体内进行了毒素gondii感染的过程。小鼠，这些动物的巨噬细胞在体外表现出对寄生虫的有缺陷的微生物活性。 p40 - / - 动物，iNOS缺乏小鼠在接种部位的急性感染和控制的寄生虫生长被体内神经化的IL-γ或IL-12所消化。然而，先前未批准的没有独立的机制在早期感染期间针对寄生虫作用。在该阶段的寄生虫膨胀和病理学中，中枢神经系统证明了一氧化氮对这种细胞内感染的保护作用是组织特异性的，而不是全身性的。
The induction by IFN-γ of reactive nitrogen intermediates has been postulated as a major mechanism of host resistance to intracellular pathogens. To formally test this hypothesis in vivo, the course of Toxoplasma gondii infection was assessed in nitric oxide synthase (iNOS)−/− mice. As expected, macrophages from these animals displayed defective microbicidal activity against the parasite in vitro. Nevertheless, in contrast to IFN-γ−/− or IL-12 p40−/− animals, iNOSdeficient mice survived acute infection and controlled parasite growth at the site of inoculation. This early resistance was ablated by neutralization of IFN-γ or IL-12 in vivo and markedly diminished by depletion of neutrophils, demonstrating the existence of previously unappreciated NO independent mechanisms operating against the parasite during early infection. By 3-4 wk post infection, however, iNOS knockout mice did succumb to T. gondii. At that stage parasite expansion and pathology were evident in the central nervous system but not the periphery suggesting that the protective role of nitric oxide against this intracellular infection is tissue specific rather than systemic.