TY - JOUR
T1 - Matrix metalloproteinases in pulmonary and central nervous system tuberculosis—A review
AU - Rohlwink, Ursula K.
AU - Walker, Naomi F.
AU - Ordonez, Alvaro A.
AU - Li, Yifan J.
AU - Tucker, Elizabeth W.
AU - Elkington, Paul T.
AU - Wilkinson, Robert J.
AU - Wilkinson, Katalin A.
N1 - Funding Information:
NFW is supported by a National Institute for Health Research Academic Clinical Lecturership, the British Infection Association, and a Starter Grant for Clinical Lecturers (The Academy of Medical Sciences UK, Wellcome, Medical Research Council UK, British Heart Foundation, Arthritis Research UK, Royal College of Physicians and Diabetes UK). AO is supported by NIH grants R01-EB020539 and R01-HL131829. EWT is supported by the Johns Hopkins All Children’s Hospital Foundation Institutional Grant Program. PTE is supported by the Medical Research Council Global Challenges Research Fund: Bioengineering to combat the tuberculosis epidemic (MR/P023754/1). RJW and KAW are supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK, the UK Medical Research Council, and the Wellcome Trust (FC00110218). RJW also receives support from the Wellcome (104803 and 203135), National Research Foundation of South Africa (96841) and National Institutes of Health (U01AI115940).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/3/2
Y1 - 2019/3/2
N2 - 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.
AB - 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.
KW - Adult
KW - Central nervous system
KW - Extracellular matrix breakdown
KW - HIV-TB-associated IRIS
KW - Lung
KW - Matrix metalloproteinases
KW - Pediatric
KW - Tuberculosis
KW - Tuberculous meningitis
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U2 - 10.3390/ijms20061350
DO - 10.3390/ijms20061350
M3 - Review article
C2 - 30889803
AN - SCOPUS:85063299070
SN - 1661-6596
VL - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 6
M1 - 1350
ER -