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首页> 外文期刊>Emerging microbes & infections. >Multidrug-resistant tuberculosis (MDR-TB) strain infection in macaques results in high bacilli burdens in airways, driving broad innate/adaptive immune responses
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Multidrug-resistant tuberculosis (MDR-TB) strain infection in macaques results in high bacilli burdens in airways, driving broad innate/adaptive immune responses

机译：猕猴中的多药耐药结核病（MDR-TB）菌株感染导致呼吸道细菌负担高，从而驱动广泛的先天/适应性免疫反应

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Tuberculosis (TB) has become the most deadly infectious diseases due to epidemics of HIV/AIDS and multidrug-resistant/extensively drug-resistant TB (MDR-/XDR-TB). Although person-to-person transmission contributes to MDR-TB, it remains unknown whether infection with MDR strains resembles infection with drug-sensitive (DS) TB strains, manipulating limited or broad immune responses. To address these questions, macaques were infected with MDR strain V791 and a drug-sensitive Erdman strain of TB. MDR bacilli burdens in the airway were significantly higher than those of the Erdman control after pulmonary exposure. This productive MDR strain infection upregulated the expression of caspase 3 in macrophages/monocytes and induced appreciable innate-like effector responses of CD3-negative lymphocytes and Ag-specific γδ T-cell subsets. Concurrently, MDR strain infection induced broad immune responses of T-cell subpopulations producing Th1, Th17, Th22, and CTL cytokines. Furthermore, MDR bacilli, like the Erdman strain, were capable of inducing typical TB disease characterized by weight loss, lymphocytopenia, and severe TB lesions. For the first time, our results suggest that MDR-TB infection acts like DS to induce high bacterial burdens in the airway (transmission advantage), innate/adaptive immune responses, and disease processes. Because nonhuman primates are biologically closer to humans than other species, our data may provide useful information for predicting the effects of primary MDR strain infection after person-to-person transmission. The findings also support the hypothesis that a vaccine or host-directed adjunctive modality that is effective for drug-sensitive TB is likely to also impact MDR-TB.
机译：由于艾滋病毒/艾滋病和多药耐药/广泛耐药结核病（MDR- / XDR-TB）的流行，结核病已成为最致命的传染病。尽管人与人之间的传播导致了耐多药结核病，但尚不清楚耐多药菌株是否类似于药物敏感性（DS）结核菌感染，从而操纵有限或广泛的免疫应答。为了解决这些问题，猕猴感染了MDR株V791和对药物敏感的TB Erdman株。肺部暴露后，气道中的MDR细菌负担明显高于Erdman对照。这种生产性MDR菌株感染可上调巨噬细胞/单核细胞中caspase 3的表达，并诱导CD3阴性淋巴细胞和Ag特异性γδT细胞亚群产生明显的先天性效应反应。同时，MDR株感染引起产生Th1，Th17，Th22和CTL细胞因子的T细胞亚群的广泛免疫反应。此外，MDR杆菌与Erdman菌株一样，能够诱发以体重减轻，淋巴细胞减少和严重TB病变为特征的典型TB疾病。我们的结果首次表明，耐多药结核病的感染类似于DS，在气道中诱导高细菌负荷（传播优势），先天/适应性免疫反应和疾病过程。由于非人类的灵长类动物在生物学上比其他物种更接近人类，因此我们的数据可能为预测人与人之间传播后原发性MDR菌株感染的影响提供有用的信息。这些发现还支持这样一种假说，即对药物敏感的结核病有效的疫苗或宿主定向辅助方式也可能会影响耐多药结核病。

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