Host-directed therapies targeting the tuberculosis granuloma stroma.

Hortle, E; Oehlers, SH

Host-directed therapies targeting the tuberculosis granuloma stroma.

Hortle, E

Oehlers, SH

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Publisher:: Oxford University Press (OUP)
Publication Type:: Journal Article
Citation:: Pathogens and disease, 2020, 78, (2)
Issue Date:: 2020-03

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Field	Value	Language
dc.contributor.author	Hortle, E https://orcid.org/0000-0001-9633-5638
dc.contributor.author	Oehlers, SH
dc.date.accessioned	2021-05-26T03:00:32Z
dc.date.available	2020-03-03
dc.date.available	2021-05-26T03:00:32Z
dc.date.issued	2020-03
dc.identifier.citation	Pathogens and disease, 2020, 78, (2)
dc.identifier.issn	2049-632X
dc.identifier.issn	2049-632X
dc.identifier.uri	http://hdl.handle.net/10453/149231
dc.description.abstract	Mycobacteria have co-evolved with their hosts resulting in pathogens adept at intracellular survival. Pathogenic mycobacteria actively manipulate infected macrophages to drive granuloma formation while subverting host cell processes to create a permissive niche. Granuloma residency confers phenotypic antimicrobial resistance by physically excluding or neutralising antibiotics. Host-directed therapies (HDTs) combat infection by restoring protective immunity and reducing immunopathology independent of pathogen antimicrobial resistance status. This review covers innovative research that has discovered 'secondary' symptoms of infection in the granuloma stroma are actually primary drivers of infection and that relieving these stromal pathologies with HDTs benefits the host. Advances in our understanding of the relationship between tuberculosis and the host vasculature, haemostatic system and extracellular matrix reorganisation are discussed. Preclinical and clinical use of HDTs against these stromal targets are summarised.
dc.format	Print
dc.language	eng
dc.publisher	Oxford University Press (OUP)
dc.relation.ispartof	Pathogens and disease
dc.relation.isbasedon	10.1093/femspd/ftaa015
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	1102 Cardiorespiratory Medicine and Haematology, 1107 Immunology, 1108 Medical Microbiology
dc.subject.classification	Microbiology
dc.subject.mesh	Animals
dc.subject.mesh	Biomarkers
dc.subject.mesh	Fibrosis
dc.subject.mesh	Granuloma
dc.subject.mesh	Hemostasis
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Molecular Targeted Therapy
dc.subject.mesh	Neovascularization, Pathologic
dc.subject.mesh	Permeability
dc.subject.mesh	Precision Medicine
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Tuberculosis
dc.subject.mesh	Granuloma
dc.subject.mesh	Fibrosis
dc.subject.mesh	Neovascularization, Pathologic
dc.subject.mesh	Hemostasis
dc.subject.mesh	Permeability
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Molecular Targeted Therapy
dc.subject.mesh	Biomarkers
dc.subject.mesh	Precision Medicine
dc.subject.mesh	Animals
dc.subject.mesh	Biomarkers
dc.subject.mesh	Fibrosis
dc.subject.mesh	Granuloma
dc.subject.mesh	Hemostasis
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Humans
dc.subject.mesh	Molecular Targeted Therapy
dc.subject.mesh	Neovascularization, Pathologic
dc.subject.mesh	Permeability
dc.subject.mesh	Precision Medicine
dc.subject.mesh	Tuberculosis
dc.title	Host-directed therapies targeting the tuberculosis granuloma stroma.
dc.type	Journal Article
utslib.citation.volume	78
utslib.location.activity	United States
utslib.for	1102 Cardiorespiratory Medicine and Haematology
utslib.for	1107 Immunology
utslib.for	1108 Medical Microbiology
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	in_progress	*
pubs.consider-herdc	false
dc.date.updated	2021-05-26T03:00:31Z
pubs.issue	2
pubs.publication-status	Published
pubs.volume	78
utslib.citation.issue	2

Abstract:

Mycobacteria have co-evolved with their hosts resulting in pathogens adept at intracellular survival. Pathogenic mycobacteria actively manipulate infected macrophages to drive granuloma formation while subverting host cell processes to create a permissive niche. Granuloma residency confers phenotypic antimicrobial resistance by physically excluding or neutralising antibiotics. Host-directed therapies (HDTs) combat infection by restoring protective immunity and reducing immunopathology independent of pathogen antimicrobial resistance status. This review covers innovative research that has discovered 'secondary' symptoms of infection in the granuloma stroma are actually primary drivers of infection and that relieving these stromal pathologies with HDTs benefits the host. Advances in our understanding of the relationship between tuberculosis and the host vasculature, haemostatic system and extracellular matrix reorganisation are discussed. Preclinical and clinical use of HDTs against these stromal targets are summarised.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/149231