Bacillus anthracis spore movement does not require a carrier cell and is not affected by lethal toxin in human lung models.
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.
Pulmonary and Critical Care Division of the Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: john-booth@ouhsc.edu.
J Leland
JL
Booth
Pulmonary and Critical Care Division of the Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: elizabeth-duggan@ouhsc.edu.
Elizabeth S
ES
Duggan
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. Electronic address: vineet-patel@ouhsc.edu.
Vineet I
VI
Patel
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: marybeth-langer@omrf.org.
Marybeth
M
Langer
Pulmonary and Critical Care Division of the Department of Internal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA. Electronic address: wenxin-wu@ouhsc.edu.
Wenxin
W
Wu
Fraunhofer Institute for Toxicology and Experimental Medicine, D-30625, Hannover, Germany. Electronic address: armin.braun@item.fraunhofer.de.
Armin
A
Braun
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA. Electronic address: mark-coggeshall@omrf.org.
K Mark
KM
Coggeshall
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. Electronic address: jordan-metcalf@ouhsc.edu.
Jordan P
JP
Metcalf
D000881:Anthrax / Q000473:pathology*; D000938:Antigen-Presenting Cells / Q000382:microbiology; D000942:Antigens, Bacterial / Q000378:metabolism*; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000378:metabolism*; D001769:Blood / Q000382:microbiology; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D008168:Lung / Q000382:microbiology*; D008198:Lymph Nodes / Q000382:microbiology*; D008962:Models, Theoretical; D009068:Movement; D009924:Organ Culture Techniques; D013171:Spores, Bacterial / Q000472:pathogenicity*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin
Anthrax toxin; Bacillus anthracis; Lethal toxin; Lung organ culture; Protective antigen