ArticleThe Journal of infectious diseases2021
Immunomodulatory Agents Combat Multidrug-Resistant Tuberculosis by Improving Antimicrobial Immunity.
Article in The Journal of infectious diseases, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Diabetes mellitus affects the treatment outcomes of drug-resistant tuberculosis: a systematic review and meta-analysis.BMC infectious diseases · 2023Pooled it
- Immune endotypes in tuberculosis: Keys to decoding disease complexity.Journal of internal medicine · 2026Review
- Case Report: Management challenges of active tuberculosis complicated by thrombocytosis and squamous cell lung carcinoma.Frontiers in oncology · 2026Article
- Autophagy andFrontiers in cellular and infection microbiology · 2026Review
- Review
- Dual GSK-3β/HDAC Inhibitors Enhance the Efficacy of Macrophages to ControlBiomolecules · 2025Article
- Clinical characteristics and prognosis of children with culture-negative osteoarticular infections: a meta-analysis based on cohort studies.EFORT open reviews · 2025Article
- Repurposed Drugs and Plant-Derived Natural Products as Potential Host-Directed Therapeutic Candidates for Tuberculosis.Biomolecules · 2024Review
- Sirtuin inhibitors reduce intracellular growth of M. tuberculosis in human macrophages via modulation of host cell immunity.Scientific reports · 2024Article
- A Supramolecular Antibiotic Targeting Drug-ResistantACS applied materials & interfaces · 2024Article
- Recognition of Mycobacterium tuberculosis by macrophage Toll-like receptor and its role in autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Advances in Diagnostics and Drug Discovery against Resistant and Latent Tuberculosis Infection.Pharmaceutics · 2023Review
- Histone deacetylase (HDAC) inhibitors- based drugs are effective to control Mycobacterium tuberculosis infection and promote the sensibility for rifampicin in MDR strain.Memorias do Instituto Oswaldo Cruz · 2023Article
- Antimicrobial peptides as drugs with double response againstFrontiers in microbiology · 2023Review
- Resistance and Susceptibility Immune Factors at Play duringPathogens (Basel, Switzerland) · 2022Review
- Emerging Non-Traditional Approaches to Combat Antibiotic Resistance.Current microbiology · 2022Review
- Characterization of Dosage Levels for In Ovo Administration of Innate Immune Stimulants for Prevention of Yolk Sac Infection in Chicks.Veterinary sciences · 2022Article
- L-GSH Supplementation in Conjunction With Rifampicin Augments the Treatment Response toFrontiers in pharmacology · 2022Article
- The Activities and Secretion of Cytokines Caused by Delamanid on Macrophages Infected by Multidrug-ResistantFrontiers in immunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMultidrug-resistant (MDR) tuberculosis has low treatment success rates, and new treatment strategies are needed. We explored whether treatment with active vitamin D3 (vitD) and phenylbutyrate (PBA) could improve conventional chemotherapy by enhancing immune-mediated eradication of Mycobacterium tuberculosis.
methodsA clinically relevant model was used consisting of human macrophages infected with M. tuberculosis isolates (n = 15) with different antibiotic resistance profiles. The antimicrobial effect of vitD+PBA, was tested together with rifampicin or isoniazid. Methods included colony-forming units (intracellular bacterial growth), messenger RNA expression analyses (LL-37, β-defensin, nitric oxide synthase, and dual oxidase 2), RNA interference (LL-37-silencing in primary macrophages), and Western blot analysis and confocal microscopy (LL-37 and LC3 protein expression).
resultsVitD+PBA inhibited growth of clinical MDR tuberculosis strains in human macrophages and strengthened intracellular growth inhibition of rifampicin and isoniazid via induction of the antimicrobial peptide LL-37 and LC3-dependent autophagy. Gene silencing of LL-37 expression enhanced MDR tuberculosis growth in vitD+PBA-treated macrophages. The combination of vitD+PBA and isoniazid were as effective in reducing intracellular MDR tuberculosis growth as a >125-fold higher dose of isoniazid alone, suggesting potent additive effects of vitD+PBA with isoniazid.
conclusionsImmunomodulatory agents that trigger multiple immune pathways can strengthen standard MDR tuberculosis treatment and contribute to next-generation individualized treatment options for patients with difficult-to-treat pulmonary tuberculosis.
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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.