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Early Events in Mycobacterium tuberculosis Infection in Cynomolgus Macaques

机译：食蟹猕猴结核分枝杆菌感染的早期事件

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Little is known regarding the early events of infection of humans with Mycobacterium tuberculosis. The cynomolgus macaque is a useful model of tuberculosis, with strong similarities to human tuberculosis. In this study, eight cynomolgus macaques were infected bronchoscopically with low-dose M. tuberculosis; clinical, immunologic, microbiologic, and pathologic events were assessed 3 to 6 weeks postinfection. Gross pathological abnormalities were observed as early as 3 weeks, including Ghon complex formation by 5 weeks postinfection. Caseous granulomas were observed in the lung as early as 4 weeks postinfection. Only caseous granulomas were observed in the lungs at these early time points, reflecting a rigorous initial response. T-cell activation (CD29 and CD69) and chemokine receptor (CXCR3 and CCR5) expression appeared localized to different anatomic sites. Activation markers were increased on cells from airways and only at modest levels on cells in peripheral blood. The priming of mycobacterium-specific T cells, characterized by the production of gamma interferon occurred slowly, with responses seen only after 4 weeks of infection. These responses were observed from T lymphocytes in blood, airways, and hilar lymph node, with responses predominantly localized to the site of infection. From these studies, we conclude that immune responses to M. tuberculosis are relatively slow in the local and peripheral compartments and that necrosis occurs surprisingly quickly during granuloma formation.
机译：关于人类感染结核分枝杆菌的早期事件知之甚少。食蟹猕猴是一种有用的结核病模型，与人类结核病有很强的相似性。在这项研究中，八支食蟹猕猴用低剂量 M支气管镜感染。结核病;在感染后3至6周评估临床，免疫，微生物和病理事件。早在3周就观察到大的病理异常，包括感染后5周形成Ghon复合物。感染后4周，在肺部观察到干酪性肉芽肿。在这些早期时间点，仅在肺部观察到干酪性肉芽肿，反映出严格的初始反应。 T细胞活化（CD29和CD69）和趋化因子受体（CXCR3和CCR5）的表达似乎位于不同的解剖部位。激活标记在气道细胞上增加，而在外周血细胞上仅适度水平。以γ-干扰素产生为特征的分枝杆菌特异性T细胞的启动缓慢发生，仅在感染4周后才可见反应。从血液，气道和肺门淋巴结中的T淋巴细胞观察到了这些反应，反应主要位于感染部位。从这些研究中，我们得出结论，对 M的免疫反应。结核在局部和周围区室相对较慢，坏死在肉芽肿形成过程中迅速发生。

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