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Modeling Pneumonic Plague in Human Precision-Cut Lung Slices Highlights a Role for the Plasminogen Activator Protease in Facilitating Type 3 Secretion
- Source :
- Infection and Immunity
- Publication Year :
- 2019
- Publisher :
- American Society for Microbiology, 2019.
-
Abstract
- Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Key to the progression of infection is the activity of the plasminogen activator protease Pla. Deletion of Pla results in a decreased Y. pestis bacterial burden in the lung and failure to progress into the lethal proinflammatory phase of disease. While a number of putative functions have been attributed to Pla, its precise role in the pathogenesis of pneumonic plague is yet to be defined.<br />Pneumonic plague is the deadliest form of disease caused by Yersinia pestis. Key to the progression of infection is the activity of the plasminogen activator protease Pla. Deletion of Pla results in a decreased Y. pestis bacterial burden in the lung and failure to progress into the lethal proinflammatory phase of disease. While a number of putative functions have been attributed to Pla, its precise role in the pathogenesis of pneumonic plague is yet to be defined. Here, we show that Pla facilitates type 3 secretion into primary alveolar macrophages but not into the commonly used THP-1 cell line. We also establish human precision-cut lung slices as a platform for modeling early host/pathogen interactions during pneumonic plague and solidify the role of Pla in promoting optimal type 3 secretion using primary human tissue with relevant host cell heterogeneity. These results position Pla as a key player in the early host/pathogen interactions that define pneumonic plague and showcase the utility of human precision-cut lung slices as a platform to evaluate pulmonary infection by bacterial pathogens.
- Subjects :
- Pneumonic plague
human precision-cut lung slices
Yersinia pestis
plasminogen activator protease
Immunology
pulmonary infection
Yersinia
Microbiology
Bubonic plague
Bacterial Adhesion
Cell Line
Type three secretion system
Proinflammatory cytokine
Mice
Plasminogen Activators
03 medical and health sciences
stomatognathic system
Macrophages, Alveolar
medicine
Animals
Humans
Lung
Pathogen
030304 developmental biology
Plague
0303 health sciences
biology
030306 microbiology
respiratory system
biology.organism_classification
medicine.disease
Molecular Pathogenesis
3. Good health
Mice, Inbred C57BL
Infectious Diseases
hPCLS
type 3 secretion
Host-Pathogen Interactions
Cytokines
Pla
Female
lipids (amino acids, peptides, and proteins)
Parasitology
pneumonic plague
Plasminogen activator
Subjects
Details
- ISSN :
- 10985522 and 00199567
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Infection and Immunity
- Accession number :
- edsair.doi.dedup.....d50f6353ed3efd2828b5453beb07edba