Department of Infectious Diseases and Immunity, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK.
Eur Respir J. 2011 Aug;38(2):456-64. doi: 10.1183/09031936.00015411. Epub 2011 Jun 9.
Tuberculosis (TB) remains a global health pandemic. Infection is spread by the aerosol route and Mycobacterium tuberculosis must drive lung destruction to be transmitted to new hosts. Such inflammatory tissue damage is responsible for morbidity and mortality in patients. The underlying mechanisms of matrix destruction in TB remain poorly understood but consideration of the lung extracellular matrix predicts that matrix metalloproteinases (MMPs) will play a central role, owing to their unique ability to degrade fibrillar collagens and other matrix components. Since we proposed the concept of a matrix degrading phenotype in TB a decade ago, diverse data implicating MMPs as key mediators in TB pathology have accumulated. We review the lines of investigation that have indicated a critical role for MMPs in TB pathogenesis, consider regulatory pathways driving MMPs and propose that inhibition of MMP activity is a realistic goal as adjunctive therapy to limit immunopathology in TB.
结核病（TB）仍然是一种全球健康大流行病。感染通过气溶胶途径传播，结核分枝杆菌必须导致肺部破坏才能传播给新宿主。这种炎症性组织损伤是导致患者发病和死亡的原因。TB 中基质破坏的潜在机制仍知之甚少，但对肺细胞外基质的考虑表明，基质金属蛋白酶（MMPs）将发挥核心作用，因为它们具有独特的降解纤维胶原和其他基质成分的能力。自从我们十年前提出 TB 中基质降解表型的概念以来，越来越多的证据表明 MMPs 是 TB 病理学中的关键介质。我们回顾了表明 MMPs 在 TB 发病机制中具有关键作用的研究线索，考虑了驱动 MMPs 的调节途径，并提出抑制 MMP 活性是作为辅助治疗限制 TB 免疫病理学的一个现实目标。
