Spatial and temporal evolution of lung granulomas in a cynomolgus macaque model of Mycobacterium tuberculosis infection.
Spatial and temporal evolution of lung granulomas in a cynomolgus macaque model of Mycobacterium tuberculosis infection.
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DOI：
10.1016/j.jrid.2018.08.001
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发表时间：
2018-09-01
期刊：
影响因子：
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通讯作者：
Lin, Philana Ling
中科院分区：
文献类型：
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作者：
Gregg, Robert W;Maiello, Pauline;Lin, Philana Ling
背景：对人类结核分枝杆菌感染后肉芽肿的进展知之甚少。使用一系列正电子发射断层扫描和计算机断层扫描（PET/CT）的动物模型，重现人类感染M。目的：我们描述了原发感染和再激活期间肉芽肿形成的空间和时间模式。方法：在原发感染和再激活期间，对食蟹猴（n = 28）进行了系列PET/CT。肺结核感染。感染后前六周内肉芽肿之间的距离（“原发性”肉芽肿）与之后发展的新肉芽肿进行比较（“继发性”肉芽肿）在初次感染、再激活和不同感染途径之间使用最近邻分析。在原发性感染过程中，在同一肺叶内原发性肉芽肿的2 cm范围内发生继发性肉芽肿的概率为80%，在免疫抑制后潜伏感染的再激活过程中也观察到了同样的模式。使用逻辑增长函数，我们能够预测的最大数量的肉芽肿，将发展在感染过程中具有良好的相关性（R2 = 0.96）。结论：这些数据提供了重要的见解的动态模式的细菌传播的最早阶段的原发性感染和再活化结核病。
BACKGROUND: Little is known about granuloma progression of Mycobacterium tuberculosis infection in humans. Using serial positron emission tomography and computed tomography (PET/CT) of an animal model that recapitulates human infection with M. tuberculosis, we are able to track lung granulomas.OBJECTIVE: We characterized the spatial and temporal pattern of granuloma formation during primary infection and reactivation.METHODS: Serial PET/CT was performed on cynomolgus macaques (n = 28) during primary and reactivation M. tuberculosis infection. Distances between granulomas during the first six weeks post infection ("primary" granulomas) were compared to new granulomas that developed afterwards ("secondary" granulomas) using nearest neighbor analysis during primary infection, reactivation and between different routes of infection.RESULTS: Secondary granulomas developed within 2 cm of a primary granuloma within the same lung lobe with 80% probability during the course of primary infection, and this same pattern was observed during reactivation of latent infection after immune suppression. Using a logistic growth function, we were able to predict the maximum number of granulomas that would develop over the course of infection with good correlation (R2 = 0.96).CONCLUSION: These data provide important insights into the dynamic patterns of bacterial dissemination during the earliest phases of primary infection and reactivation tuberculosis.