Disparate Tuberculosis Disease Development in Macaque Species Is Associated With Innate Immunity
Disparate Tuberculosis Disease Development in Macaque Species Is Associated With Innate Immunity
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DOI：
10.3389/fimmu.2019.02479
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发表时间：
2019-11-01
影响因子：
7.3
通讯作者：
Verreck, Frank A. W.
中科院分区：
文献类型：
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作者：
Dijkman, Karin;Vervenne, Richard A. W.;Verreck, Frank A. W.
虽然结核病继续困扰着人类，但结核病发生的免疫学机制仍然不完全清楚。结核病研究的高级临床前模型包括恒河猴和食蟹猴(分别是恒河猴和食蟹猴)，恒河猴通常比食蟹猴更容易患上急性进行性结核病。为了确定哪些免疫机制导致这种不同的疾病发展，我们描述了两个物种在实验性肺结核分枝杆菌(Mtb)感染后的广泛的先天和适应性反应，包括局部和外周。虽然T细胞和抗体反应似乎无法区分，但我们发现恒河猴外周血单核细胞的抗炎偏斜，以及食蟹猴局部致炎细胞因子的释放与不同的结核病疾病结局相关。重要的是，这些差异在感染前和感染后早期都可以检测到。这项工作表明，感染前和感染后早期的炎症和先天免疫状态对结核病感染的结局有重要影响。
While tuberculosis continues to afflict mankind, the immunological mechanisms underlying TB disease development are still incompletely understood. Advanced preclinical models for TB research include both rhesus and cynomolgus macaques (Macaca mulatta and Macaca fascicularis, respectively), with rhesus typically being more susceptible to acute progressive TB disease than cynomolgus macaques. To determine which immune mechanisms are responsible for this dissimilar disease development, we profiled a broad range of innate and adaptive responses, both local and peripheral, following experimental pulmonary Mycobacterium tuberculosis (Mtb) infection of both species. While T-cell and antibody responses appeared indistinguishable, we identified anti-inflammatory skewing of peripheral monocytes in rhesus and a more prominent local pro-inflammatory cytokine release profile in cynomolgus macaques associated with divergent TB disease outcome. Importantly, these differences were detectable both before and early after infection. This work shows that inflammatory and innate immune status prior to and at early stages after infection, critically affects outcome of TB infection.