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首页> 外文期刊>Infection and immunity >Identification of Mycobacterium tuberculosis Counterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening
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Identification of Mycobacterium tuberculosis Counterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening

机译：通过差异筛选鉴定免疫缺陷小鼠中的结核分枝杆菌抗免疫（cim）突变体

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Tuberculosis (TB) is characterized by lifetime persistence of Mycobacterium tuberculosis. Despite the induction of a vigorous host immune response that curtails disease progression in the majority of cases, the organism is not eliminated. Subsequent immunosuppression can lead to reactivation after a prolonged period of clinical latency. Thus, while it is clear that protective immune mechanisms are engaged during M. tuberculosis infection, it also appears that the pathogen has evolved effective countermechanisms. Genetic studies with animal infection models and with patients have revealed a key role for the cytokine gamma interferon (IFN-γ) in resistance to TB. IFN-γ activates a large number of antimicrobial pathways. Three of these IFN-γ-dependent mechanisms have been implicated in defense against M. tuberculosis: inducible nitric oxide synthase (iNOS), phagosome oxidase (phox), and the phagosome-associated GTPase LRG-47. In order to identify bacterial genes that provide protection against specific host immune pathways, we have developed the strategy of differential signature-tagged transposon mutagenesis. Using this approach we have identified three M. tuberculosis genes that are essential for progressive M. tuberculosis growth and rapid lethality in iNOS-deficient mice but not in IFN-γ-deficient mice. We propose that these genes are involved in pathways that allow M. tuberculosis to counter IFN-γ-dependent immune mechanisms other than iNOS.
机译：结核病（TB）的特征是结核分枝杆菌（emembacterium tuberculosis）的终生持久性。尽管在大多数情况下诱导了强烈的宿主免疫反应，从而抑制了疾病的进展，但并未消除这种生物。长时间的临床潜伏期后，随后的免疫抑制可导致重新激活。因此，尽管很清楚在 M期间参与了保护性免疫机制。结核病感染后，病原体似乎已经进化出有效的抗药性。对动物感染模型和患者进行的遗传研究表明，细胞因子γ干扰素（IFN-γ）在抗结核病方面具有关键作用。 IFN-γ激活大量的抗菌途径。这些干扰素-γ依赖机制中的三种已被证明对 M具有防御作用。结核病：诱导型一氧化氮合酶（iNOS），吞噬体氧化酶（phox）和与吞噬体相关的GTPase LRG-47。为了鉴定对特定宿主免疫途径具有保护作用的细菌基因，我们开发了差异标记标签转座子诱变的策略。使用这种方法，我们确定了三个 M。进行性M病必不可少的结核基因。 iNOS缺陷小鼠的肺结核生长和快速致死率，而IFN-γ缺陷小鼠则没有。我们建议这些基因参与允许 M的途径。抵抗iNOS以外的IFN-γ依赖性免疫机制。

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