UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Tezera, LB; Bielecka, MK; Chancellor, A; Reichmann, MT; Al Shammari, B; Brace, P; Batty, A; ... Elkington, PT; + view all (2017) Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model. eLife , 6 , Article e21283. 10.7554/eLife.21283. Green open access

[thumbnail of Tezara_Dissection_host-pathogen_interaction.pdf]
Preview
Text
Tezara_Dissection_host-pathogen_interaction.pdf - Published version

Download (3MB) | Preview

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.

Type: Article
Title: Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model
Open access status: An open access version is available from UCL Discovery
DOI: 10.7554/eLife.21283
Publisher version: https://doi.org/10.7554/eLife.21283
Language: English
Additional information: Copyright © Tezera et al. This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/1536537
Downloads since deposit
0Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item