Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review

Ursula K. Rohlwink, Naomi F. Walker, Alvaro Ordonez Suarez, Yifan J. Li, Elizabeth Tucker, Paul T. Elkington, Robert J. Wilkinson, Katalin A. Wilkinson

Research output: Contribution to journalReview article

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.

Original languageEnglish (US)
JournalInternational journal of molecular sciences
Volume20
Issue number6
DOIs
StatePublished - Mar 18 2019

Fingerprint

Central Nervous System Tuberculosis
tuberculosis
central nervous system
Neurology
Matrix Metalloproteinases
Lung
matrices
meningitis
Meningeal Tuberculosis
Tuberculosis
human immunodeficiency virus
Brain
lungs
brain
Immune Reconstitution Inflammatory Syndrome
HIV
breakdown
Pediatrics
blood-brain barrier
Pathology

Keywords

  • adult
  • central nervous system
  • extracellular matrix breakdown
  • HIV-TB-associated IRIS
  • lung
  • matrix metalloproteinases
  • pediatric
  • tuberculosis
  • tuberculous meningitis

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review. / Rohlwink, Ursula K.; Walker, Naomi F.; Ordonez Suarez, Alvaro; Li, Yifan J.; Tucker, Elizabeth; Elkington, Paul T.; Wilkinson, Robert J.; Wilkinson, Katalin A.

In: International journal of molecular sciences, Vol. 20, No. 6, 18.03.2019.

Research output: Contribution to journalReview article

Rohlwink, Ursula K. ; Walker, Naomi F. ; Ordonez Suarez, Alvaro ; Li, Yifan J. ; Tucker, Elizabeth ; Elkington, Paul T. ; Wilkinson, Robert J. ; Wilkinson, Katalin A. / Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 6.
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