Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex.
Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex.
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DOI：
10.1080/21505594.2018.1491255
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发表时间：
2018
期刊：
影响因子：
5.2
通讯作者：
Langford PR
中科院分区：
文献类型：
--
作者：
Li Y;Spiropoulos J;Cooley W;Khara JS;Gladstone CA;Asai M;Bossé JT;Robertson BD;Newton SM;Langford PR
长期以来，动物模型一直用于结核病研究，以了解疾病的发病机制，并评估新的疫苗候选人和抗分枝杆菌药物。然而，所有这些都有局限性，没有一种动物模型可以模拟人类中所见的分枝杆菌发病机制的所有方面。重要的是，最常用的模型小鼠通常不会形成肉芽肿，而肉芽肿是结核感染的标志。因此，迫切需要开发新的替代体内模型。昆虫幼虫，大蜡螟已越来越多地被用作一个成功的，简单的，广泛可用的和成本效益的模型来研究微生物感染。在这里，我们报告的第一次，G。大梅隆菌可用作结核分枝杆菌复合体成员的感染模型。我们证明了G.用不同的生物发光牛分枝杆菌BCG lux接种物感染的大蜡螟存活，并证明14天以上的分枝杆菌发光抑制。感染G.大蜡螟吞噬血细胞表现出M. Bovis BCG lux在肉芽肿样结构中的作用，以及M.随着时间的推移，牛BCG lux，具有潜伏性结核感染的特征。结果表明，G.梅隆菌可以作为一种替代宿主来研究分枝杆菌感染的发病机制，并揭示宿主-分枝杆菌相互作用，包括潜伏性结核感染。
Animal models have long been used in tuberculosis research to understand disease pathogenesis and to evaluate novel vaccine candidates and anti-mycobacterial drugs. However, all have limitations and there is no single animal model which mimics all the aspects of mycobacterial pathogenesis seen in humans. Importantly mice, the most commonly used model, do not normally form granulomas, the hallmark of tuberculosis infection. Thus there is an urgent need for the development of new alternative in vivo models. The insect larvae, Galleria mellonella has been increasingly used as a successful, simple, widely available and cost-effective model to study microbial infections. Here we report for the first time that G. mellonella can be used as an infection model for members of the Mycobacterium tuberculosis complex. We demonstrate a dose-response for G. mellonella survival infected with different inocula of bioluminescent Mycobacterium bovis BCG lux, and demonstrate suppression of mycobacterial luminesence over 14 days. Histopathology staining and transmission electron microscopy of infected G. mellonella phagocytic haemocytes show internalization and aggregation of M. bovis BCG lux in granuloma-like structures, and increasing accumulation of lipid bodies within M. bovis BCG lux over time, characteristic of latent tuberculosis infection. Our results demonstrate that G. mellonella can act as a surrogate host to study the pathogenesis of mycobacterial infection and shed light on host-mycobacteria interactions, including latent tuberculosis infection.
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