Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 6, Pages -Publisher
MDPI
DOI: 10.3390/ijms20061350
Keywords
tuberculosis; matrix metalloproteinases; tuberculous meningitis; HIV-TB-associated IRIS; extracellular matrix breakdown; adult; pediatric; lung; central nervous system
Funding
- National Institute for Health Research Academic Clinical Lecturership
- British Infection Association
- Academy of Medical Sciences UK
- Wellcome
- Medical Research Council UK
- British Heart Foundation
- Arthritis Research UK
- Royal College of Physicians
- NIH [R01-EB020539, R01-HL131829]
- Johns Hopkins All Children's Hospital Foundation Institutional Grant Program
- Medical Research Council Global Challenges Research Fund: Bioengineering to combat the tuberculosis epidemic [MR/P023754/1]
- Francis Crick Institute - Cancer Research UK
- UK Medical Research Council
- Wellcome Trust [FC00110218]
- Wellcome [104803, 203135]
- National Research Foundation of South Africa [96841]
- National Institutes of Health [U01AI115940]
- Diabetes UK
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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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