ArticlePLoS pathogens2015
Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers.
What it found
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Who cites it
143 citing papers in PubMed, 225 citations in OpenAlex.
- Azithromycin as Host-Directed Therapy for Pulmonary Tuberculosis: A Randomized Pilot Trial.The Journal of infectious diseases · 2025Trial
- Doxycycline host-directed therapy in human pulmonary tuberculosis.The Journal of clinical investigation · 2021Trial
- Pathogenesis of Tuberculosis: Interplay Between Host Antituberculosis Immunity and Immune Evasion Strategies ofMedComm · 2026Review
- Neutrophils and tuberculosis - insights into immunobiology and pathogenesis.Molecular biology reports · 2026Review
- NETosis associates with human TB lung tissue destruction and disease pathogenesis.EMBO molecular medicine · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Towards host-directed therapy: The role of matrix metalloproteinases in the immunopathogenesis of tuberculosis.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026Review
- The host immune response to Mycobacterium tuberculosis determining protection or disease progression.Nature immunology · 2026Review
- Context-specific roles for IL-17 in tuberculosis.PLoS pathogens · 2026Review
- Conserved neutrophil degranulation transcripts in HIV-TB coinfected children across East and Southern Africa.Communications medicine · 2026Article
- Review
- Article
- A co-evolutionary perspective on humans andeLife · 2026Review
- Necro-mosaic: a lesion-aware framework for testing programmed cell-death-associated mechanisms in tuberculosis.Frontiers in immunology · 2026Review
- Inflammatory biomarkers as predictors of paradoxical reaction in tubercular meningitis: a prospective observational study.BMJ neurology open · 2026Article
- Serum cytokine analysis in cavitary and non-cavitary pulmonary Mycobacterium avium complex disease: a cross-sectional study.BMC infectious diseases · 2025Article
- Immune transcriptomic differences in paediatric patients with SARS-CoV-2 compared to other lower respiratory tract infections.bioRxiv : the preprint server for biology · 2025Article
- Pre-treatment blood cell counts and inflammatory markers predict the radiologic severity of post-tuberculosis lung disease.BMC infectious diseases · 2025Article
- MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.Journal of neuroinflammation · 2025Article
- The Intricate Process of Calcification in Granuloma Formation and the Complications FollowingBiomolecules · 2025Review
83 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 8 institutions in 4 countries.
Funding
Abstract
Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.