Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish

Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish.

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Item Type: Article
Status: Published
Official URL:
Journal or Publication Title: The Journal of Infectious Diseases
Volume: 220
Number: 3
Page Range: pp. 524-534
Date: 2019
Divisions: Immune-Vascular Interactions
Depositing User: General Admin
Identification Number: 10.1093/infdis/jiz110
ISSN: 0022-1899
Date Deposited: 21 Dec 2020 23:05

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 antiplatelet mode of action.

Methods: In this study, we utilize the zebrafish-Mycobacterium marinum model to show mycobacteria drive host hemostasis 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.

Conclusions: Our study illuminates platelet activation as an efficacious target of aspirin, a widely available and affordable host-directed therapy candidate for tuberculosis.

Keywords: clotting; hemostasis; innate immunity; mycobacterial infection.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail:

Hortle, Elinor
Johnson, Khelsey E
Johansen, Matt D
Nguyen, Tuong
Shavit, Jordan A
Britton, Warwick J
Tobin, David M
Oehlers, Stefan H
Last Modified: 21 Dec 2020 23:05

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