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首页> 外文期刊>Infection and immunity >Defective Nitric Oxide Effector Functions Lead to Extreme Susceptibility of Trypanosoma cruzi-Infected Mice Deficient in Gamma Interferon Receptor or Inducible Nitric Oxide Synthase
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Defective Nitric Oxide Effector Functions Lead to Extreme Susceptibility of Trypanosoma cruzi-Infected Mice Deficient in Gamma Interferon Receptor or Inducible Nitric Oxide Synthase

机译：一氧化氮效应子功能缺陷导致克鲁格氏锥虫感染小鼠的γ干扰素受体或诱导型一氧化氮合酶缺乏症的极易感性。

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Trypanosoma cruzi, the causative agent of Chagas’ disease, induces an innate and adaptive host immune response during the acute phase of infection. These responses were analyzed by comparing mouse lines deficient for the gamma interferon (IFN-γ) receptor (IFN-γR?/?) or deficient for inducible nitric oxide synthase (iNOS?/?). Both lines were highly susceptible, with similar and dramatically increased parasite burdens and severe histopathology and were incapable of surviving even very low doses, exhibiting similar mortality kinetics. This pathophysiological correlation has a common cause, since both mutant mouse strains were unable to respond to infection by producing nitric oxide (NO) with the consequence that mutant macrophages had impaired trypanocidal activities. These in vivo and subsequent in vitro studies further demonstrated that an IFN-γ-dependent pathway of iNOS induction is crucial for efficient NO production and mandatory for resisting acute infection with T. cruzi. Despite this defect, both mutant mouse strains had a rather normal proinflammatory cytokine response (interleukin-12 [IL-12], IFN-γ, IL-6), with the exception of an impaired tumor necrosis factor alpha and IL-1α response in IFN-γR?/? mice, demonstrating that only the latter two cytokines are dependent on IFN-γ activation. Moreover, polarization of T cells in type 1 and type 2 T-helper (Th1/Th2) and cytotoxic T (Tc1/Tc2) cells as well as T. cruzi-specific antibody responses were normal in IFN-γR?/? mice, demonstrating that IFN-γ is not necessary for the promotion of T-cell differentiation and T. cruzi-specific antibody responses.
机译：恰加斯氏病的病原体）或缺乏诱导型一氧化氮合酶（iNOS α/β< / sup>）。两种品系均极易感，具有相似且显着增加的寄生虫负担和严重的组织病理学，即使在非常低的剂量下也无法存活，表现出相似的死亡率动力学。这种病理生理相关性有一个共同的原因，因为两种突变小鼠品系均无法通过产生一氧化氮（NO）来应对感染，结果突变巨噬细胞损害了锥虫杀虫活性。这些体内和随后的体外研究进一步证明，iNOS诱导的IFN-γ依赖性途径对于有效产生NO至关重要，对于抵抗 T的急性感染也是必不可少的。 cruzi 。尽管存在这一缺陷，但两种突变小鼠品系均具有相当正常的促炎细胞因子反应（白介素12 [IL-12]，IFN-γ，IL-6），但肿瘤坏死因子α和IL-1α反应受损。 IFN-γR？/？小鼠，证明只有后两种细胞因子依赖于IFN-γ激活。此外，1型和2型T辅助（Th1 / Th2）和细胞毒性T（Tc1 / Tc2）细胞以及 T的T细胞极化。在IFN-γR？/？小鼠中，cruzi 特异性抗体反应正常，这表明IFN-γ并不是促进T细胞分化和 T所必需的。 Cruzi特异的抗体反应。

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