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Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model

Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model
Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model
Cell 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.
1-19
Tezera, Liku B.
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Bielecka, Magdalena K.
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Chancellor, Andrew
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Reichmann, Michela T.
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Al Shammari, Basim
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Brace, Patience
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Batty, Alex
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Tocheva, Anna
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Jogai, Sanjay
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Marshall, Ben G.
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Tebruegge, Marc
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Jayasinghe, Suwan N.
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Mansour, Salah
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Elkington, Paul T.
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Tezera, Liku B.
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Bielecka, Magdalena K.
90391ea3-aa1f-4104-a893-568c138718a2
Chancellor, Andrew
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Reichmann, Michela T.
a2c90ce6-ed4a-43e1-827e-f7ddde682a47
Al Shammari, Basim
607a5b92-cab1-4cd4-8ce0-04e433a32b02
Brace, Patience
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Batty, Alex
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Tocheva, Anna
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Jogai, Sanjay
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Marshall, Ben G.
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Tebruegge, Marc
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Jayasinghe, Suwan N.
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Mansour, Salah
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Elkington, Paul T.
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Tezera, Liku B., Bielecka, Magdalena K., Chancellor, Andrew, Reichmann, Michela T., Al Shammari, Basim, Brace, Patience, Batty, Alex, Tocheva, Anna, Jogai, Sanjay, Marshall, Ben G., Tebruegge, Marc, Jayasinghe, Suwan N., Mansour, Salah and Elkington, Paul T. (2017) Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model. eLife, 6 (e21283), 1-19. (doi:10.7554/eLife.21283).

Record type: Article

Abstract

Cell 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.

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More information

Accepted/In Press date: 5 January 2017
e-pub ahead of print date: 7 January 2017
Published date: 7 January 2017
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 404532
URI: https://eprints.soton.ac.uk/id/eprint/404532
PURE UUID: 7e84d873-f59d-4f9a-8e37-39705bff2ebc
ORCID for Liku B. Tezera: ORCID iD orcid.org/0000-0002-7898-6709
ORCID for Salah Mansour: ORCID iD orcid.org/0000-0002-5982-734X
ORCID for Paul T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 11 Jan 2017 12:15
Last modified: 10 Dec 2019 01:41

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