Multidrug-resistant tuberculosis (MDR-TB) strain infection in macaques results in high bacilli burdens in airways, driving broad innate/adaptive immune responses.,Emerging Microbes & Infections

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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.
Emerging Microbes & Infections ( IF 8.4 ) Pub Date : 2018-Dec-12 , DOI: 10.1038/s41426-018-0213-z
Enzhuo Yang _{1,

2} , Rui Yang _{1,

3} , Ming Guo ₄ , Dan Huang ₂ , Wandang Wang ₂ , Zhuoran Zhang ₂ , Crystal Chen ₂ , Feifei Wang ₅ , Wenzhe Ho ₄ , Ling Shen ₂ , Heping Xiao ₁ , Zheng W Chen ₂ , Hongbo Shen _{1,

3}

Affiliation

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.

中文翻译：

猕猴的耐多药结核病 (MDR-TB) 菌株感染会导致气道中的高杆菌负荷，从而驱动广泛的先天/适应性免疫反应。

由于艾滋病毒/艾滋病和耐多药/广泛耐药结核病（MDR-/XDR-TB）的流行，结核病（TB）已成为最致命的传染病。尽管人与人之间的传播会导致耐多药结核病，但尚不清楚耐多药菌株的感染是否类似于药物敏感（DS）结核菌株的感染，从而操纵有限或广泛的免疫反应。为了解决这些问题，猕猴感染了 MDR V791 菌株和药物敏感的 Erdman 结核菌株。肺部暴露后，气道中的 MDR 杆菌负荷显着高于 Erdman 对照。这种高效的 MDR 菌株感染上调了巨噬细胞/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 γδ T 细胞亚群明显的先天样效应反应。同时，MDR 菌株感染诱导 T 细胞亚群产生广泛的免疫反应，产生 Th1、Th17、Th22 和 CTL 细胞因子。此外，MDR 杆菌与 Erdman 菌株一样，能够诱发典型的结核病，其特征是体重减轻、淋巴细胞减少和严重结核病灶。我们的结果首次表明，耐多药结核病感染的作用与 DS 类似，可诱导气道中的高细菌负荷（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际传播后原发性 MDR 菌株感染的影响提供有用的信息。研究结果还支持这样的假设：对药物敏感结核病有效的疫苗或针对宿主的辅助疗法也可能对耐多药结核病产生影响。

更新日期：2019-01-26

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