Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish.

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

Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish.

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

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Publisher:: Oxford University Press (OUP)
Publication Type:: Journal Article
Citation:: The Journal of infectious diseases, 2019, 220, (3), pp. 524-534
Issue Date:: 2019-07

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Field	Value	Language
dc.contributor.author	Hortle, E
dc.contributor.author	Johnson, KE
dc.contributor.author	Johansen, MD
dc.contributor.author	Nguyen, T
dc.contributor.author	Shavit, JA
dc.contributor.author	Britton, WJ
dc.contributor.author	Tobin, DM
dc.contributor.author	Oehlers, SH
dc.date.accessioned	2020-05-22T01:11:06Z
dc.date.available	2019-03-07
dc.date.available	2020-05-22T01:11:06Z
dc.date.issued	2019-07
dc.identifier.citation	The Journal of infectious diseases, 2019, 220, (3), pp. 524-534
dc.identifier.issn	0022-1899
dc.identifier.issn	1537-6613
dc.identifier.uri	http://hdl.handle.net/10453/140883
dc.description.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 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.
dc.format	Print
dc.language	eng
dc.publisher	Oxford University Press (OUP)
dc.relation.ispartof	The Journal of infectious diseases
dc.relation.isbasedon	10.1093/infdis/jiz110
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	06 Biological Sciences, 11 Medical and Health Sciences
dc.subject.classification	Microbiology
dc.subject.mesh	Blood Platelets
dc.subject.mesh	Macrophages
dc.subject.mesh	Animals
dc.subject.mesh	Zebrafish
dc.subject.mesh	Mycobacterium marinum
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Granuloma
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Platelet Aggregation Inhibitors
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Blood Platelets
dc.subject.mesh	Macrophages
dc.subject.mesh	Animals
dc.subject.mesh	Zebrafish
dc.subject.mesh	Mycobacterium marinum
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Granuloma
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Platelet Aggregation Inhibitors
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Animals
dc.subject.mesh	Bacterial Proteins
dc.subject.mesh	Blood Platelets
dc.subject.mesh	Disease Models, Animal
dc.subject.mesh	Granuloma
dc.subject.mesh	Macrophages
dc.subject.mesh	Mycobacterium Infections, Nontuberculous
dc.subject.mesh	Mycobacterium marinum
dc.subject.mesh	Platelet Aggregation Inhibitors
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Zebrafish
dc.title	Thrombocyte Inhibition Restores Protective Immunity to Mycobacterial Infection in Zebrafish.
dc.type	Journal Article
utslib.citation.volume	220
utslib.location.activity	United States
utslib.for	06 Biological Sciences
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
pubs.consider-herdc	false
dc.date.updated	2020-05-22T01:10:59Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	220
utslib.start-page	524
utslib.citation.issue	3

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 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.

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http://hdl.handle.net/10453/140883