Booth J Leland, Duggan Elizabeth S, Patel Vineet I, Langer Marybeth, Wu Wenxin, Braun Armin, Coggeshall K Mark, Metcalf Jordan P
Pulmonary and Critical Care Division of the Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Pulmonary and Critical Care Division of the Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA; Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Microbes Infect. 2016 Oct;18(10):615-626. doi: 10.1016/j.micinf.2016.06.004. Epub 2016 Jun 16.
The lung is the entry site for Bacillus anthracis in inhalation anthrax, the most deadly form of the disease. Spores escape from the alveolus to regional lymph nodes, germinate and enter the circulatory system to cause disease. The roles of carrier cells and the effects of B. anthracis toxins in this process are unclear. We used a human lung organ culture model to measure spore uptake by antigen presenting cells (APC) and alveolar epithelial cells (AEC), spore partitioning between these cells, and the effects of B. anthracis lethal toxin and protective antigen. We repeated the study in a human A549 alveolar epithelial cell model. Most spores remained unassociated with cells, but the majority of cell-associated spores were in AEC, not in APC. Spore movement was not dependent on internalization, although the location of internalized spores changed in both cell types. Spores also internalized in a non-uniform pattern. Toxins affected neither transit of the spores nor the partitioning of spores into AEC and APC. Our results support a model of spore escape from the alveolus that involves spore clustering with transient passage through intact AEC. However, subsequent transport of spores by APC from the lung to the lymph nodes may occur.
肺是吸入性炭疽中炭疽杆菌的进入部位，吸入性炭疽是该疾病最致命的形式。孢子从肺泡逸出至局部淋巴结，萌发并进入循环系统引发疾病。在此过程中，载体细胞的作用以及炭疽杆菌毒素的影响尚不清楚。我们使用人肺器官培养模型来测量抗原呈递细胞（APC）和肺泡上皮细胞（AEC）对孢子的摄取、孢子在这些细胞之间的分配以及炭疽杆菌致死毒素和保护性抗原的影响。我们在人A549肺泡上皮细胞模型中重复了该研究。大多数孢子未与细胞结合，但大多数与细胞结合的孢子存在于AEC中，而非APC中。孢子的移动不依赖于内化作用，尽管内化孢子在两种细胞类型中的位置均发生了变化。孢子也以不均匀的模式内化。毒素既不影响孢子的转运，也不影响孢子在AEC和APC中的分配。我们的结果支持一种孢子从肺泡逸出的模型，该模型涉及孢子聚集并短暂穿过完整的AEC。然而，随后APC可能会将孢子从肺转运至淋巴结。
