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

Liku B. Tezera; Magdalena K. Bielecka; Andrew Chancellor; Michaela T. Reichmann; Basim Al Shammari; Patience Brace; Alex Batty; Annie Tocheva; Sanjay Jogai; Ben G. Marshall; Marc Tebruegge; Suwan N. Jayasinghe; Salah Mansour; Paul T. Elkington

doi:10.7554/eLife.21283

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

Liku B. Tezera, Magdalena K. Bielecka, Andrew Chancellor, Michaela T. Reichmann, Basim Al Shammari, Patience Brace, Alex Batty, Annie Tocheva, Sanjay Jogai, Ben G. Marshall, Marc Tebruegge, Suwan N. Jayasinghe, Salah Mansour, Paul T. Elkington

Research output: Contribution to journal › Article › peer-review

62 Scopus citations

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.

Original language	English
Article number	e21283
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.21283
State	Published - 7 Jan 2017
Externally published	Yes

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Tezera, L. B., Bielecka, M. K., Chancellor, A., Reichmann, M. T., Shammari, B. A., 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, Article e21283. https://doi.org/10.7554/eLife.21283

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

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.",

author = "Tezera, {Liku B.} and Bielecka, {Magdalena K.} and Andrew Chancellor and Reichmann, {Michaela T.} and Shammari, {Basim Al} and Patience Brace and Alex Batty and Annie Tocheva and Sanjay Jogai and Marshall, {Ben G.} and Marc Tebruegge and Jayasinghe, {Suwan N.} and Salah Mansour and Elkington, {Paul T.}",

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AU - Bielecka, Magdalena K.

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AU - Shammari, Basim Al

AU - Brace, Patience

AU - Batty, Alex

AU - Tocheva, Annie

AU - Jogai, Sanjay

AU - Marshall, Ben G.

AU - Tebruegge, Marc

AU - Jayasinghe, Suwan N.

AU - Mansour, Salah

AU - Elkington, Paul T.

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

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