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In vitro granuloma models of tuberculosis: potential and challenges

In vitro granuloma models of tuberculosis: potential and challenges
In vitro granuloma models of tuberculosis: potential and challenges
Despite intensive research efforts, several fundamental disease processes for tuberculosis (TB) remain poorly understood. A central enigma is that host immunity is necessary to control disease yet promotes transmission by causing lung immunopathology. Our inability to distinguish these processes makes it challenging to design rational novel interventions. Elucidating basic immune mechanisms likely requires both in vivo and in vitro analyses, since Mycobacterium tuberculosis is a highly specialized human pathogen. The classic immune response is the TB granuloma organized in three dimensions within extracellular matrix. Several groups are developing cell culture granuloma models. In January 2018, NIAID convened a workshop, entitled “3-D Human in vitro TB Granuloma Model” to advance the field. Here, we summarize the arguments for developing advanced TB cell culture models and critically review those currently available. We discuss how integrating complementary approaches, specifically organoids and mathematical modeling, can maximize progress, and conclude by discussing future challenges and opportunities.
0022-1899
1858–1866
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Lerm, Maria
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Kapoor, Nidhi
d747d8a6-73e8-42e7-8292-8d3ed5a61af6
Mahon, Robert
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Pienaar, Elsje
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Huh, Dongeun
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Kaushal, Deepak
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Schlesinger, Larry
d6ec1d94-ca3d-4fb3-bc27-edb52d653279
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Lerm, Maria
b11db1fb-3d4a-46b6-9db2-51e7e42b2889
Kapoor, Nidhi
d747d8a6-73e8-42e7-8292-8d3ed5a61af6
Mahon, Robert
0bda7c57-f2b9-4405-a525-90e32526d4c0
Pienaar, Elsje
df0329fb-ae8d-4bff-9384-4e30532cbf6e
Huh, Dongeun
8b5c39d6-86c6-4f88-9c0f-b962d492d425
Kaushal, Deepak
c3e3d322-fd6d-4022-a842-04396ac07210
Schlesinger, Larry
d6ec1d94-ca3d-4fb3-bc27-edb52d653279

Elkington, Paul, Lerm, Maria, Kapoor, Nidhi, Mahon, Robert, Pienaar, Elsje, Huh, Dongeun, Kaushal, Deepak and Schlesinger, Larry (2019) In vitro granuloma models of tuberculosis: potential and challenges. Journal of Infectious Diseases, 219 (12), 1858–1866. (doi:10.1093/infdis/jiz020).

Record type: Review

Abstract

Despite intensive research efforts, several fundamental disease processes for tuberculosis (TB) remain poorly understood. A central enigma is that host immunity is necessary to control disease yet promotes transmission by causing lung immunopathology. Our inability to distinguish these processes makes it challenging to design rational novel interventions. Elucidating basic immune mechanisms likely requires both in vivo and in vitro analyses, since Mycobacterium tuberculosis is a highly specialized human pathogen. The classic immune response is the TB granuloma organized in three dimensions within extracellular matrix. Several groups are developing cell culture granuloma models. In January 2018, NIAID convened a workshop, entitled “3-D Human in vitro TB Granuloma Model” to advance the field. Here, we summarize the arguments for developing advanced TB cell culture models and critically review those currently available. We discuss how integrating complementary approaches, specifically organoids and mathematical modeling, can maximize progress, and conclude by discussing future challenges and opportunities.

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Elkington Granuloma modeling complete - Accepted Manuscript
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More information

Accepted/In Press date: 3 January 2019
e-pub ahead of print date: 31 March 2019
Published date: 15 June 2019
Additional Information: Editor's choice

Identifiers

Local EPrints ID: 427167
URI: http://eprints.soton.ac.uk/id/eprint/427167
ISSN: 0022-1899
PURE UUID: a045da97-96fb-41fb-a441-315b46e0d568
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 04 Jan 2019 17:30
Last modified: 26 Nov 2021 05:51

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Contributors

Author: Paul Elkington ORCID iD
Author: Maria Lerm
Author: Nidhi Kapoor
Author: Robert Mahon
Author: Elsje Pienaar
Author: Dongeun Huh
Author: Deepak Kaushal
Author: Larry Schlesinger

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