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The extracellular matrix regulates granuloma necrosis in tuberculosis

The extracellular matrix regulates granuloma necrosis in tuberculosis
The extracellular matrix regulates granuloma necrosis in tuberculosis
A central tenet of tuberculosis (TB) pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of TB pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human TB granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase-1 causes caseous necrosis, the pathological hallmark of human TB. Collagen destruction is the principal pathological difference to wild type mice, whereas the release of pro-inflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of TB granuloma formation utilising bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed by LDH release, propidium iodide staining and total viable cells. Taken together, these findings suggest that collagen destruction is an initial event in TB immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction.
tuberculosis, extracellular matrix, matrix metalloprotease, immunopathology
0022-1899
463-473
Al shammari, B.
e036b46d-0aec-45a6-882f-c23b71891f45
Shiomi, T.
76a3576a-129c-48f1-97d3-7dba2994b30a
Tezera, L.
c5598dbf-23a8-4934-96a4-7c783bf9e776
Bielecka, Magdalena
90391ea3-aa1f-4104-a893-568c138718a2
Workman, V.
020aa458-07c5-4f26-bdc3-19a5af2148d5
Sathyamoorthy, T.
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Mauri, F.
1e417ed6-d2ab-45a2-bed2-6b5d7ef78dae
Jayasinghe, S.N.
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Robertson, B.D.
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D'Armiento, J.
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Friedland, J.S.
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Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Al shammari, B.
e036b46d-0aec-45a6-882f-c23b71891f45
Shiomi, T.
76a3576a-129c-48f1-97d3-7dba2994b30a
Tezera, L.
c5598dbf-23a8-4934-96a4-7c783bf9e776
Bielecka, Magdalena
90391ea3-aa1f-4104-a893-568c138718a2
Workman, V.
020aa458-07c5-4f26-bdc3-19a5af2148d5
Sathyamoorthy, T.
83d53741-7a15-4b98-8000-d66f377c2fa1
Mauri, F.
1e417ed6-d2ab-45a2-bed2-6b5d7ef78dae
Jayasinghe, S.N.
45ee9e92-565c-4485-829a-1c94f4837ba9
Robertson, B.D.
669e6a52-8c52-4c62-a2b6-3c5d3d835f90
D'Armiento, J.
a7fd2275-4323-4715-adab-c50a26628267
Friedland, J.S.
e64a7af8-b969-4426-82e6-5ebe819799c9
Elkington, P.T.
60828c7c-3d32-47c9-9fcc-6c4c54c35a15

Al shammari, B., Shiomi, T., Tezera, L., Bielecka, Magdalena, Workman, V., Sathyamoorthy, T., Mauri, F., Jayasinghe, S.N., Robertson, B.D., D'Armiento, J., Friedland, J.S. and Elkington, P.T. (2015) The extracellular matrix regulates granuloma necrosis in tuberculosis. The Journal of Infectious Diseases, 212 (3), 463-473. (PMID:25676469)

Record type: Article

Abstract

A central tenet of tuberculosis (TB) pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism of TB pathology and demonstrate that collagen destruction may be a critical initial event, causing caseous necrosis as opposed to resulting from it. In human TB granulomas, regions of extracellular matrix destruction map to areas of caseous necrosis. In mice, transgenic expression of human matrix metalloproteinase-1 causes caseous necrosis, the pathological hallmark of human TB. Collagen destruction is the principal pathological difference to wild type mice, whereas the release of pro-inflammatory cytokines does not differ, demonstrating that collagen breakdown may lead to cell death and caseation. To investigate this hypothesis, we developed a 3-dimensional cell culture model of TB granuloma formation utilising bioelectrospray technology. Collagen improved survival of Mycobacterium tuberculosis-infected cells analyzed by LDH release, propidium iodide staining and total viable cells. Taken together, these findings suggest that collagen destruction is an initial event in TB immunopathology, leading to caseous necrosis and compromising the immune response, revealing a previously unappreciated role for the extracellular matrix in regulating the host-pathogen interaction.

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Accepted/In Press date: 29 January 2015
e-pub ahead of print date: 12 February 2015
Published date: 1 August 2015
Keywords: tuberculosis, extracellular matrix, matrix metalloprotease, immunopathology
Organisations: Faculty of Medicine, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 374376
URI: https://eprints.soton.ac.uk/id/eprint/374376
ISSN: 0022-1899
PURE UUID: 74c17f0a-1947-4abd-b843-5671bebaffcb
ORCID for L. Tezera: ORCID iD orcid.org/0000-0002-7898-6709
ORCID for P.T. Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 13 Feb 2015 15:21
Last modified: 06 Jun 2018 12:28

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Contributors

Author: B. Al shammari
Author: T. Shiomi
Author: L. Tezera ORCID iD
Author: V. Workman
Author: T. Sathyamoorthy
Author: F. Mauri
Author: S.N. Jayasinghe
Author: B.D. Robertson
Author: J. D'Armiento
Author: J.S. Friedland
Author: P.T. Elkington ORCID iD

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