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 fact...

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Bibliographic Details
Published in:International journal of molecular sciences 2019-03, Vol.20 (6), p.1350
Main Authors: Rohlwink, Ursula K, Walker, Naomi F, Ordonez, Alvaro A, Li, Yifan J, Tucker, Elizabeth W, Elkington, Paul T, Wilkinson, Robert J, Wilkinson, Katalin A
Format: Article
Language:English
Subjects:
Biomarkers - metabolism
Central nervous system
Critical care
Drugs
Granulomas
Health sciences
Humans
Infectious diseases
Matrix metalloproteinases
Matrix Metalloproteinases - metabolism
Medicine
Meningitis
Models, Biological
Observatories
Pathogenesis
Pediatrics
Review
Tuberculosis
Tuberculosis, Central Nervous System - enzymology
Tuberculosis, Central Nervous System - therapy
Tuberculosis, Meningeal - enzymology
Tuberculosis, Meningeal - therapy
Tuberculosis, Pulmonary - enzymology
Tuberculosis, Pulmonary - therapy
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Summary: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 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20061350