ArticlePloS one2011
Phosphodiesterase 4 inhibition reduces innate immunity and improves isoniazid clearance of Mycobacterium tuberculosis in the lungs of infected mice.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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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
42 citing papers in PubMed, 72 citations in OpenAlex.
- DRTB-HDT: a randomized controlled trial of two adjunctive host-directed therapies in rifampin-resistant tuberculosis.BMC infectious diseases · 2025Trial
- 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
- Differential regulation of monocyte oxidative burst by isoniazid in healthy and latent tuberculosis-infected subjects.Frontiers in pharmacology · 2026Article
- Inhibition of host PARP1 contributes to the anti-inflammatory and antitubercular activity of pyrazinamide.Nature communications · 2023Article
- Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus.Frontiers in immunology · 2023Review
- A phosphodiesterase-4 inhibitor reduces lung inflammation and fibrosis in a hamster model of SARS-CoV-2 infection.Frontiers in immunology · 2023Article
- Recent Advances in Host-Directed Therapies for Tuberculosis and Malaria.Frontiers in cellular and infection microbiology · 2022Review
- Therapeutic host-directed strategies to improve outcome in tuberculosis.Mucosal immunology · 2020Review
- Tuberculosis and targeted synthetic or biologic DMARDs, beyond tumor necrosis factor inhibitors.Therapeutic advances in musculoskeletal disease · 2020Review
- Calcitriol enhances pyrazinamide treatment of murine tuberculosis.Chinese medical journal · 2019Article
- Thalidomide and Phosphodiesterase 4 Inhibitors as Host Directed Therapeutics for Tuberculous Meningitis: Insights From the Rabbit Model.Frontiers in cellular and infection microbiology · 2019Review
- Dynamic balance of pro- and anti-inflammatory signals controls disease and limits pathology.Immunological reviews · 2018Review
- Combined chemical genetics and data-driven bioinformatics approach identifies receptor tyrosine kinase inhibitors as host-directed antimicrobials.Nature communications · 2018Article
- Host-directed therapies for bacterial and viral infections.Nature reviews. Drug discovery · 2018Review
- Article
- Host sirtuin 1 regulates mycobacterial immunopathogenesis and represents a therapeutic target against tuberculosis.Science immunology · 2017Article
- Host-Directed Therapeutic Strategies for Tuberculosis.Frontiers in medicine · 2017Review
- Targeting dendritic cells to accelerate T-cell activation overcomes a bottleneck in tuberculosis vaccine efficacy.Nature communications · 2016Article
- Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model.EBioMedicine · 2016Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the leading infectious disease causes of morbidity and mortality worldwide. Though current antibiotic regimens can cure the disease, treatment requires at least six months of drug therapy. One reason for the long duration of therapy is that the currently available TB drugs were selected for their ability to kill replicating organisms and are less effective against subpopulations of non-replicating persistent bacilli. Evidence from in vitro models of Mtb growth and mouse infection studies suggests that host immunity may provide some of the environmental cues that drive Mtb towards non-replicating persistence. We hypothesized that selective modulation of the host immune response to modify the environmental pressure on the bacilli may result in better bacterial clearance during TB treatment. For this proof of principal study, we compared bacillary clearance from the lungs of Mtb-infected mice treated with the anti-TB drug isoniazid (INH) in the presence and absence of an immunomodulatory phosphodiesterase 4 inhibitor (PDE4i), CC-3052. The effects of CC-3052 on host global gene expression, induction of cytokines, and T cell activation in the lungs of infected mice were evaluated. We show that CC-3052 modulates the innate immune response without causing generalized immune suppression. Immune modulation combined with INH treatment improved bacillary clearance and resulted in smaller granulomas and less lung pathology, compared to treatment with INH alone. This novel strategy of combining anti-TB drugs with an immune modulating molecule, if applied appropriately to patients, may shorten the duration of TB treatment and improve clinical outcome.
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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.