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
(This article belongs to the Special Issue Bacterial Exotoxins and Their Impact on Host–Pathogen Interaction in Animals and Humans)
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
▼
Show Figures
Figure 1
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
- Supplementary File 1:
PDF-Document (PDF, 518 KiB)
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 StylePatel, 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
Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.
Search more from Scilit
