PUBLICATION
Thrombocyte inhibition restores protective immunity to mycobacterial infection in zebrafish
- Authors
- Hortle, E., Johnson, K.E., Johansen, M.D., Nguyen, T., Shavit, J.A., Britton, W.J., Tobin, D.M., Oehlers, S.H.
- ID
- ZDB-PUB-190317-7
- Date
- 2019
- Source
- The Journal of infectious diseases 220(3): 524-534 (Journal)
- Registered Authors
- Hortle, Elinor, Oehlers, Stefan, Shavit, Jordan, Tobin, David
- Keywords
- Mycobacterial infection, clotting, hemostasis, innate immunity
- MeSH Terms
-
- Animals
- Bacterial Proteins/immunology
- Blood Platelets/drug effects*
- Blood Platelets/immunology*
- Disease Models, Animal
- Granuloma/drug therapy
- Granuloma/immunology
- Granuloma/microbiology
- Macrophages/drug effects
- Macrophages/immunology
- Macrophages/microbiology
- Mycobacterium Infections, Nontuberculous/drug therapy*
- Mycobacterium Infections, Nontuberculous/immunology*
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium marinum/drug effects
- Mycobacterium marinum/immunology*
- Platelet Aggregation Inhibitors/pharmacology
- Tuberculosis/drug therapy
- Tuberculosis/immunology
- Tuberculosis/microbiology
- Zebrafish/immunology*
- Zebrafish/microbiology*
- PubMed
- 30877311 Full text @ J. Infect. Dis.
Citation
Hortle, E., Johnson, K.E., Johansen, M.D., Nguyen, T., Shavit, J.A., Britton, W.J., Tobin, D.M., Oehlers, S.H. (2019) Thrombocyte inhibition restores protective immunity to mycobacterial infection in zebrafish. The Journal of infectious diseases. 220(3):524-534.
Abstract
Background Infection-induced thrombocytosis is a clinically important complication of tuberculosis infection. Recent studies have highlighted the utility of aspirin as a host-directed therapy modulating the inflammatory response to infection, but have not investigated the possibility that the effect of aspirin is related to an anti-platelet mode of action.
Methods Here we utilise the zebrafish-Mycobacterium marinum model to show mycobacteria drive host haemostasis through the formation of granulomas. Treatment of infected zebrafish with aspirin markedly reduced mycobacterial burden. This effect is reproduced by treatment with platelet-specific glycoprotein IIb/IIIa inhibitors demonstrating a detrimental role for infection-induced thrombocyte activation.
Results We find that the reduction in mycobacterial burden is dependent on macrophages and granuloma formation providing the first in vivo experimental evidence that infection-induced platelet activation compromises protective host immunity to mycobacterial infection.
Conclusion Our study illuminates platelet activation as an efficacious target of aspirin, a widely available and affordable host-directed therapy candidate for tuberculosis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping