Neuroscience Institute, University of Cape Town, Faculty of Health Sciences, Anzio Road, Observatory 7925, South Africa.
TB Centre and Department of Clinical Research, London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, UK.
Int J Mol Sci. 2019 Mar 18;20(6):1350. doi: 10.3390/ijms20061350.
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.
结核病（TB）仍然是全球单一最大的传染病死因，每年导致近 200 万人死亡，超过 1000 万人患病。基质金属蛋白酶（MMPs）是一类具有多种生理作用的蛋白水解酶，被认为是导致结核病传播的关键因素。它们参与肺部细胞外基质的分解，随后将细菌释放到气道中。有证据表明，MMPs 在中枢神经系统（CNS）结核病中也发挥作用，因为它们有助于血脑屏障的破坏，并与结核性脑膜炎（TBM）成人患者的不良预后相关。然而，在儿科 TBM 中，数据表明 MMPs 可能在发育中大脑的病理和恢复中发挥作用。MMPs 在肺部和大脑中 HIV-TB 相关免疫重建炎症综合征中也具有重要作用，其调节提供了潜在的新的治疗途径。这是一篇关于 MMP 在成人和儿童肺部和中枢神经系统结核病以及与 HIV 合并感染中的最新研究的综述。我们总结了 MMP 研究的不同方法，并讨论了 MMP 抑制以减少免疫病理学的转化意义。
