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dc.contributor.authorTezera, LB
dc.contributor.authorBielecka, MK
dc.contributor.authorChancellor, A
dc.contributor.authorReichmann, MT
dc.contributor.authorAl Shammari, B
dc.contributor.authorBrace, P
dc.contributor.authorBatty, A
dc.contributor.authorTocheva, A
dc.contributor.authorJogai, S
dc.contributor.authorMarshall, BG
dc.contributor.authorTebruegge, M
dc.contributor.authorJayasinghe, SN
dc.contributor.authorMansour, S
dc.contributor.authorElkington, PT
dc.date.accessioned2021-02-04T02:10:22Z
dc.date.available2021-02-04T02:10:22Z
dc.date.issued2017-01-07
dc.identifier.citationTezera, L. B., Bielecka, M. K., Chancellor, A., Reichmann, M. T., Al Shammari, B., Brace, P., Batty, A., Tocheva, A., Jogai, S., Marshall, B. G., Tebruegge, M., Jayasinghe, S. N., Mansour, S. & Elkington, P. T. (2017). Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model. ELIFE, 6, https://doi.org/10.7554/eLife.21283.
dc.identifier.issn2050-084X
dc.identifier.urihttp://hdl.handle.net/11343/259595
dc.description.abstractCell biology differs between traditional cell culture and 3-dimensional (3-D) systems, and is modulated by the extracellular matrix. Experimentation in 3-D presents challenges, especially with virulent pathogens. Mycobacterium tuberculosis (Mtb) kills more humans than any other infection and is characterised by a spatially organised immune response and extracellular matrix remodelling. We developed a 3-D system incorporating virulent mycobacteria, primary human blood mononuclear cells and collagen-alginate matrix to dissect the host-pathogen interaction. Infection in 3-D led to greater cellular survival and permitted longitudinal analysis over 21 days. Key features of human tuberculosis develop, and extracellular matrix integrity favours the host over the pathogen. We optimised multiparameter readouts to study emerging therapeutic interventions: cytokine supplementation, host-directed therapy and immunoaugmentation. Each intervention modulates the host-pathogen interaction, but has both beneficial and harmful effects. This methodology has wide applicability to investigate infectious, inflammatory and neoplastic diseases and develop novel drug regimes and vaccination approaches.
dc.languageEnglish
dc.publisherELIFE SCIENCES PUBLICATIONS LTD
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleDissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model
dc.typeJournal Article
dc.identifier.doi10.7554/eLife.21283
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titleeLife
melbourne.source.volume6
dc.rights.licenseCC BY
melbourne.elementsid1218533
melbourne.contributor.authorTebruegge, Marc
dc.identifier.eissn2050-084X
melbourne.accessrightsOpen Access


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