Matrix Metalloproteinases in Tuberculosis Pathogenesis
Summary
Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that orchestrate the degradation of extracellular matrix components during Mycobacterium tuberculosis infection. In pulmonary tuberculosis, dysregulated MMP activity drives tissue destruction, facilitating cavity formation and bacterial dissemination. Host cells such as macrophages, neutrophils and epithelial cells secrete distinct MMPs in response to inflammatory and hypoxic cues. Regulation of MMP expression involves signalling pathways including nuclear factor κB, p38 MAP kinase and hypoxia-inducible factor 1α, balanced by tissue inhibitors of metalloproteinases (TIMPs). Excessive MMP activity disrupts granuloma integrity, promoting caseation and fibrosis, while modulating immune responses. Understanding the spatial and temporal dynamics of MMP expression has underscored their dual role in host defence and immunopathology, highlighting MMPs as biomarkers of disease severity and targets for adjunctive host-directed therapies aimed at preserving tissue architecture and improving drug delivery.
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Matrix Metalloproteinases in Tuberculosis Pathogenesis publication trend
The graph below shows the total number of articles in matrix metalloproteinases in tuberculosis pathogenesis across all publications each year (not limited to Nature Index journals).
Technical terms
Granuloma: A structured aggregate of immune cells formed in response to persistent pathogens, characterised by a necrotic core surrounded by immune and stromal cells.
Extracellular Matrix (ECM): A network of proteins and polysaccharides that provides structural support to tissues and regulates cell behaviour.
Matrix Metalloproteinase (MMP): A family of zinc-dependent enzymes that degrade components of the ECM, implicated in tissue remodelling and disease pathology.
Tissue Inhibitor of Metalloproteinase (TIMP): Endogenous proteins that bind MMPs to regulate their proteolytic activity and maintain matrix integrity.
References
- Spatial transcriptomic sequencing reveals immune microenvironment features of Mycobacterium tuberculosis granulomas in lung and omentum. Theranostics (2024).
- An acidic microenvironment in Tuberculosis increases extracellular matrix degradation by regulating macrophage inflammatory responses. PLOS Pathogens (2023).
- Automated quantitative assay of fibrosis characteristics in tuberculosis granulomas. Frontiers in Microbiology (2024).
- Matrix metalloproteinases: Expression, regulation and role in the immunopathology of tuberculosis. Cell Proliferation (2019).
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