Journal article
Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function
Infection and immunity, Vol.80(12), pp.4374-4387
12/01/2012
DOI: 10.1128/IAI.01011-12
PMCID: PMC3497415
PMID: 23027535
Abstract
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.
Details
- Title: Subtitle
- Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function
- Creators
- Marybeth Langer - University of Oklahoma Health Sciences CenterElizabeth Stewart Duggan - University of Oklahoma Health Sciences CenterJohn Leland Booth - University of Oklahoma Health Sciences CenterVineet Indrajit Patel - University of Oklahoma Health Sciences CenterRyan A. Zander - University of Oklahoma Health Sciences CenterRobert Silasi-Mansat - Oklahoma Medical Research FoundationVijay Ramani - University of Oklahoma Health Sciences CenterTibor Zoltan Veres - University of TurkuFrauke Prenzler - Fraunhofer Institute for Toxicology and Experimental MedicineKatherina Sewald - Fraunhofer Institute for Toxicology and Experimental MedicineDaniel M. Williams - Civil Aerospace Medical InstituteKenneth Mark Coggeshall - Oklahoma Medical Research FoundationShanjana Awasthi - University of Oklahoma Health Sciences CenterFlorea Lupu - Oklahoma Medical Research FoundationDennis Burian - Civil Aerospace Medical InstituteJimmy Dale Ballard - University of Oklahoma Health Sciences CenterArmin Braun - Fraunhofer Institute for Toxicology and Experimental MedicineJordan Patrick Metcalf - University of Oklahoma Health Sciences Center
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, Vol.80(12), pp.4374-4387
- DOI
- 10.1128/IAI.01011-12
- PMID
- 23027535
- PMCID
- PMC3497415
- NLM abbreviation
- Infect Immun
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Publisher
- American Society for Microbiology
- Language
- English
- Date published
- 12/01/2012
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297433802771
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