Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hortle, E; Johnson, KE; Johansen, MD; Nguyen, T; Shavit, JA; Britton, WJ; Tobin, DM; Oehlers, SH

Published Date

  • July 2, 2019

Published In

Volume / Issue

  • 220 / 3

Start / End Page

  • 524 - 534

PubMed ID

  • 30877311

Pubmed Central ID

  • 30877311

Electronic International Standard Serial Number (EISSN)

  • 1537-6613

Digital Object Identifier (DOI)

  • 10.1093/infdis/jiz110

Language

  • eng

Conference Location

  • United States