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Open AccessArticle

Anthrax Edema and Lethal Toxins Differentially Target Human Lung and Blood Phagocytes

1
Department of Medicine, Pulmonary, Critical Care & Sleep Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
2
Department of Biostatistics, Virginia Commonwealth University, Richmond, VA 23298, USA
3
Department of Microbiology and Immunology, the University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA
4
Veterans Affairs Medical Center, Oklahoma City, OK 73104, USA
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(7), 464; https://doi.org/10.3390/toxins12070464
Received: 29 June 2020 / Revised: 14 July 2020 / Accepted: 15 July 2020 / Published: 20 July 2020
Bacillus anthracis, the causative agent of inhalation anthrax, is a serious concern as a bioterrorism weapon. The vegetative form produces two exotoxins: Lethal toxin (LT) and edema toxin (ET). We recently characterized and compared six human airway and alveolar-resident phagocyte (AARP) subsets at the transcriptional and functional levels. In this study, we examined the effects of LT and ET on these subsets and human leukocytes. AARPs and leukocytes do not express high levels of the toxin receptors, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2). Less than 20% expressed surface TEM8, while less than 15% expressed CMG2. All cell types bound or internalized protective antigen, the common component of the two toxins, in a dose-dependent manner. Most protective antigen was likely internalized via macropinocytosis. Cells were not sensitive to LT-induced apoptosis or necrosis at concentrations up to 1000 ng/mL. However, toxin exposure inhibited B. anthracis spore internalization. This inhibition was driven primarily by ET in AARPs and LT in leukocytes. These results support a model of inhalation anthrax in which spores germinate and produce toxins. ET inhibits pathogen phagocytosis by AARPs, allowing alveolar escape. In late-stage disease, LT inhibits phagocytosis by leukocytes, allowing bacterial replication in the bloodstream. View Full-Text
Keywords: anthrax; lethal toxin; edema toxin; spores; pathogenesis; human lung; macrophage(s); dendritic cell(s); phagocyte(s); macropinocytosis anthrax; lethal toxin; edema toxin; spores; pathogenesis; human lung; macrophage(s); dendritic cell(s); phagocyte(s); macropinocytosis
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MDPI and ACS Style

Patel, V.I.; Booth, J.L.; Dozmorov, M.; Brown, B.R.; Metcalf, J.P. Anthrax Edema and Lethal Toxins Differentially Target Human Lung and Blood Phagocytes. Toxins 2020, 12, 464. https://doi.org/10.3390/toxins12070464

AMA Style

Patel VI, Booth JL, Dozmorov M, Brown BR, Metcalf JP. Anthrax Edema and Lethal Toxins Differentially Target Human Lung and Blood Phagocytes. Toxins. 2020; 12(7):464. https://doi.org/10.3390/toxins12070464

Chicago/Turabian Style

Patel, Vineet I.; Booth, J. L.; Dozmorov, Mikhail; Brown, Brent R.; Metcalf, Jordan P. 2020. "Anthrax Edema and Lethal Toxins Differentially Target Human Lung and Blood Phagocytes" Toxins 12, no. 7: 464. https://doi.org/10.3390/toxins12070464

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