Bacillus anthracis lethal toxin reduces human alveolar epithelial barrier function.
نویسندگان
چکیده
The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness.
منابع مشابه
Human Alveolar Epithelial Barrier Function Bacillus anthracis Lethal Toxin Reduces
Published Ahead of Print 1 October 2012. 2012, 80(12):4374. DOI: 10.1128/IAI.01011-12. Infect. Immun. Patrick Metcalf Burian, Jimmy Dale Ballard, Armin Braun and Jordan Mark Coggeshall, Shanjana Awasthi, Florea Lupu, Dennis Prenzler, Katherina Sewald, Daniel M. Williams, Kenneth Silasi-Mansat, Vijay Ramani, Tibor Zoltan Veres, Frauke Booth, Vineet Indrajit Patel, Ryan A. Zander, Robert Marybeth...
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ورودعنوان ژورنال:
- Infection and immunity
دوره 80 12 شماره
صفحات -
تاریخ انتشار 2012