ArticlePloS one2018
Adjunct antibody administration with standard treatment reduces relapse rates in a murine tuberculosis model of necrotic granulomas.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Proapoptotic Bcl-2 inhibitor as potential host directed therapy for pulmonary tuberculosis.Nature communications · 2025Article
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
- Proapoptotic Bcl-2 inhibitor as host directed therapy for pulmonary tuberculosis.Research square · 2024Article
- Potential of Neuroinflammation-Modulating Strategies in Tuberculous Meningitis: Targeting Microglia.Aging and disease · 2024Review
- Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide.Nature communications · 2023Article
- Review
- IL-10 Modulation Increases Pyrazinamide's Antimycobacterial Efficacy against Mycobacterium tuberculosis Infection in Mice.ImmunoHorizons · 2023Article
- Immunologic and imaging signatures in post tuberculosis lung disease.Tuberculosis (Edinburgh, Scotland) · 2022Review
- The Association between Circulating microRNAs and the Risk of Active Disease Development from Latent Tuberculosis Infection: a Nested Case-Control Study.Microbiology spectrum · 2022Article
- Host-directed therapy to combat mycobacterial infections.Immunological reviews · 2021Review
- Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis.Frontiers in immunology · 2021Review
- Profiling the mRNA and miRNA in Peripheral Blood Mononuclear Cells in Subjects with Active Tuberculosis.Infection and drug resistance · 2020Article
- Matrix metalloproteinases: Expression, regulation and role in the immunopathology of tuberculosis.Cell proliferation · 2019Review
- Treatment-Shortening Effect of a Novel Regimen Combining Clofazimine and High-Dose Rifapentine in Pathologically Distinct Mouse Models of Tuberculosis.Antimicrobial agents and chemotherapy · 2019Article
- Matrix Metalloproteinases in Pulmonary and Central Nervous System Tuberculosis-A Review.International journal of molecular sciences · 2019Review
- Matrix Metalloproteinase Inhibition in a Murine Model of Cavitary Tuberculosis Paradoxically Worsens Pathology.The Journal of infectious diseases · 2019Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Matrix metalloproteinase (MMP)-9 is a zinc-dependent protease associated with early immune responses to Mycobacterium tuberculosis infection, macrophage recruitment and granuloma formation. We evaluated whether adjunctive inhibition of MMP-9 could improve the response to standard TB treatment in a mouse model that develops necrotic lesions. Six weeks after an aerosol infection with M. tuberculosis, C3HeB/FeJ mice received standard TB treatment (12 weeks) comprising rifampin, isoniazid and pyrazinamide alone or in combination with either anti-MMP-9 antibody, etanercept (positive control) or isotype antibody (negative control) for 6 weeks. Anti-MMP-9 and the isotype control had comparable high serum exposures and expected terminal half-life. The relapse rate in mice receiving standard TB treatment was 46.6%. Compared to the standard TB treatment, relapse rates in animals that received adjunctive treatments with anti-MMP-9 antibody or etanercept were significantly decreased to 25.9% (P = 0.006) and 29.8% (P = 0.019) respectively, but were not different from the arm that received the isotype control antibody (25.9%). Immunostaining demonstrated localization of MMP-9 primarily in macrophages in both murine and human lung tissues infected with M. tuberculosis, suggesting the importance of MMP-9 in TB pathogenesis. These data suggest that the relapse rates in M. tuberculosis-infected mice may be non-specifically improved by administration of antibodies in conjunction with standard TB treatments. Future studies are needed to evaluate the mechanism(s) leading to improved outcomes with adjunctive antibody treatments.
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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.