ArticleAmerican journal of respiratory and critical care medicine2012
Doxycycline and HIV infection suppress tuberculosis-induced matrix metalloproteinases.
Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 140 citations in OpenAlex.
- Doxycycline host-directed therapy in human pulmonary tuberculosis.The Journal of clinical investigation · 2021Trial
- Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.PLoS pathogens · 2017Trial
- Matrix metalloproteinases and tissue damage in HIV-tuberculosis immune reconstitution inflammatory syndrome.European journal of immunology · 2014Trial
- Trial
- Proteomic Immune Signatures of Severe HIV-Associated Tuberculosis in Sub-Saharan Africa: A Prospective, Multicenter Analysis From Uganda.Critical care explorations · 2026Observational
- 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
- Post-TB lung disease: pathogenesis, host-directed therapies, and the C3HeB/FeJ model for pre-clinical advances.Infection and immunity · 2026Review
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- Immunotherapy for tuberculosis: current landscape, mechanistic insights, and translational perspectives.Frontiers in immunology · 2026Review
- Article
- Plasma proteomics for biomarker discovery in childhood tuberculosis.Nature communications · 2025Article
- Collagen-targeted PET/CT imaging of tuberculosis patients.The European respiratory journal · 2025Article
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- Inflammatory profiles in sputum and blood of people with TB with and without HIV coinfection.Tuberculosis (Edinburgh, Scotland) · 2025Article
- Physiological stage-dependent effects ofFrontiers in microbiology · 2025Article
- Identification of Hub Genes and Prediction of Targeted Drugs for Rheumatoid Arthritis and Idiopathic Pulmonary Fibrosis.Biochemical genetics · 2024Article
- Pathogenesis of Post-Tuberculosis Lung Disease: Defining Knowledge Gaps and Research Priorities at the Second International Post-Tuberculosis Symposium.American journal of respiratory and critical care medicine · 2024Review
- Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.Aging and disease · 2024Review
- Article
- Review
29 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 5 countries.
Funding
Abstract
rationaleTuberculosis kills more than 1.5 million people per year, and standard treatment has remained unchanged for more than 30 years. Tuberculosis (TB) drives matrix metalloproteinase (MMP) activity to cause immunopathology. In advanced HIV infection, tissue destruction is reduced, but underlying mechanisms are poorly defined and no current antituberculous therapy reduces host tissue damage.
objectivesTo investigate MMP activity in patients with TB with and without HIV coinfection and to determine the potential of doxycycline to inhibit MMPs and decrease pathology.
methodsConcentrations of MMPs and cytokines were analyzed by Luminex array in a prospectively recruited cohort of patients. Modulation of MMP secretion and Mycobacterium tuberculosis growth by doxycycline was studied in primary human cells and TB-infected guinea pigs. MEASUREMENTS AND MAIN
resultsHIV coinfection decreased MMP concentrations in induced sputum of patients with TB. MMPs correlated with clinical markers of tissue damage, further implicating dysregulated protease activity in TB-driven pathology. In contrast, cytokine concentrations were no different. Doxycycline, a licensed MMP inhibitor, suppressed TB-dependent MMP-1 and -9 secretion from primary human macrophages and epithelial cells by inhibiting promoter activation. In the guinea pig model, doxycycline reduced lung TB colony forming units after 8 weeks in a dose-dependent manner compared with untreated animals, and in vitro doxycycline inhibited mycobacterial proliferation.
conclusionsHIV coinfection in patients with TB reduces concentrations of immunopathogenic MMPs. Doxycycline decreases MMP activity in a cellular model and suppresses mycobacterial growth in vitro and in guinea pigs. Adjunctive doxycycline therapy may reduce morbidity and mortality in TB.
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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.