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Matrix metalloproteinases in pulmonary and central nervous system tuberculosis – a review

Matrix metalloproteinases in pulmonary and central nervous system tuberculosis – a review
Matrix metalloproteinases in pulmonary and central nervous system tuberculosis – a review
Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology
1422-0067
1350
Rohlwink, Ursula
a880ef68-9503-46fd-bd83-3731dafe9fdd
Walker, Naomi
cb8a626a-4f9b-485b-9533-f551584c0108
Ordonez, Alvaro
d8e14cd2-2a91-421c-9141-31aed83fc62b
Li, Joshua
2c0754ae-234c-4046-aa78-1e4bf95d726e
Tucker, Elizabeth
2d16a41f-b1de-4882-b547-2dd88d6ec42e
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Wilkinson, Robert
6968bb11-0079-45f4-85e3-e0cd45ef82b1
Wilkinson, Katalin
0e7ce2c3-64ba-4c89-b381-a4d7665b4d3e
Rohlwink, Ursula
a880ef68-9503-46fd-bd83-3731dafe9fdd
Walker, Naomi
cb8a626a-4f9b-485b-9533-f551584c0108
Ordonez, Alvaro
d8e14cd2-2a91-421c-9141-31aed83fc62b
Li, Joshua
2c0754ae-234c-4046-aa78-1e4bf95d726e
Tucker, Elizabeth
2d16a41f-b1de-4882-b547-2dd88d6ec42e
Elkington, Paul
60828c7c-3d32-47c9-9fcc-6c4c54c35a15
Wilkinson, Robert
6968bb11-0079-45f4-85e3-e0cd45ef82b1
Wilkinson, Katalin
0e7ce2c3-64ba-4c89-b381-a4d7665b4d3e

Rohlwink, Ursula, Walker, Naomi, Ordonez, Alvaro, Li, Joshua, Tucker, Elizabeth, Elkington, Paul, Wilkinson, Robert and Wilkinson, Katalin (2019) Matrix metalloproteinases in pulmonary and central nervous system tuberculosis – a review. International Journal of Molecular Sciences, 20 (6), 1350. (doi:10.3390/ijms20061350).

Record type: Review

Abstract

Tuberculosis (TB) remains the single biggest infectious cause of death globally, claiming almost two million lives and causing disease in over 10 million individuals annually. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes with various physiological roles implicated as key factors contributing to the spread of TB. They are involved in the breakdown of lung extracellular matrix and the consequent release of Mycobacterium tuberculosis bacilli into the airways. Evidence demonstrates that MMPs also play a role in central nervous system (CNS) tuberculosis, as they contribute to the breakdown of the blood brain barrier and are associated with poor outcome in adults with tuberculous meningitis (TBM). However, in pediatric TBM, data indicate that MMPs may play a role in both pathology and recovery of the developing brain. MMPs also have a significant role in HIV-TB-associated immune reconstitution inflammatory syndrome in the lungs and the brain, and their modulation offers potential novel therapeutic avenues. This is a review of recent research on MMPs in pulmonary and CNS TB in adults and children and in the context of co-infection with HIV. We summarize different methods of MMP investigation and discuss the translational implications of MMP inhibition to reduce immunopathology

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MMP review final - Version of Record
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Accepted/In Press date: 3 March 2019
Published date: 18 March 2019

Identifiers

Local EPrints ID: 429423
URI: http://eprints.soton.ac.uk/id/eprint/429423
ISSN: 1422-0067
PURE UUID: 5d65042e-e082-406b-935c-f9c36c9d8579
ORCID for Paul Elkington: ORCID iD orcid.org/0000-0003-0390-0613

Catalogue record

Date deposited: 27 Mar 2019 17:30
Last modified: 26 Nov 2021 02:59

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Contributors

Author: Ursula Rohlwink
Author: Naomi Walker
Author: Alvaro Ordonez
Author: Joshua Li
Author: Elizabeth Tucker
Author: Paul Elkington ORCID iD
Author: Robert Wilkinson
Author: Katalin Wilkinson

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