Trial reportJournal of immunology (Baltimore, Md. : 1950)2014
All-trans retinoic acid-triggered antimicrobial activity against Mycobacterium tuberculosis is dependent on NPC2.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Association of variant vitamin statuses and tuberculosis development: a systematic review and meta-analysis.Annals of medicine · 2024Pooled it
- Effects of zinc and vitamin A supplementation on prognostic markers and treatment outcomes of adults with pulmonary tuberculosis: a systematic review and meta-analysis.BMJ global health · 2022Pooled it
- Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.PLoS medicine · 2019Pooled it
- The Impact of Vitamin A Deficiency on Tuberculosis Progression.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Vitamin A and D Deficiencies Associated With Incident Tuberculosis in HIV-Infected Patients Initiating Antiretroviral Therapy in Multinational Case-Cohort Study.Journal of acquired immune deficiency syndromes (1999) · 2017Trial
- Identification of a spatially organized TREM2-associated permissive macrophage niche in human pulmonary tuberculosis alveolar pneumonia.Nature communications · 2026Article
- Mechanisms, Modulation, and Mitigation: Dietary-Gut Microbiome Strategies Against Antibiotic Resistance.Probiotics and antimicrobial proteins · 2026Review
- Immune-adaptive pathogen variation reveals targetable mediators of gram-positive bacterial killing in macrophages.Science advances · 2026Article
- Systems-level characterization of EGFR kinase inhibitors reveals heterogeneous effects on Mtb-macrophage interactions.bioRxiv : the preprint server for biology · 2025Article
- Immunomodulation by bacterial products promotes innate signatures favorable to macrophage responses in tuberculosis infection.Frontiers in immunology · 2025Article
- Activation of nuclear receptors correlates with tuberculosis severity and is a target for host-directed therapy.Frontiers in cellular and infection microbiology · 2025Article
- LncRNA SNHG16 Inhibits IntracellularACS omega · 2024Article
- The Endogenous Retinoic Acid Receptor Pathway Is Exploited by Mycobacterium tuberculosis during Infection, Both In Vitro and In Vivo.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Association of Micronutrients with Tuberculosis Development in HIV Infected Patients.Indian journal of clinical biochemistry : IJCB · 2023Article
- A terpene nucleoside from M. tuberculosis induces lysosomal lipid storage in foamy macrophages.The Journal of clinical investigation · 2023Article
- Retinol-Loaded Poly(vinyl alcohol)-Based Hydrogels as Suitable Biomaterials with Antimicrobial Properties for the Proliferation of Mesenchymal Stem Cells.International journal of molecular sciences · 2022Article
- Host-Directed Therapies for Tuberculosis.Pathogens (Basel, Switzerland) · 2022Review
- Fat-soluble vitamins: updated review of their role and orchestration in human nutrition throughout life cycle with sex differences.Nutrition & metabolism · 2022Review
- Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis.Pharmaceutics · 2022Article
- CRISPR Interference Reveals That All-mBio · 2022Article
7 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
7 authors at 2 institutions in 1 country.
Funding
Abstract
A role for vitamin A in host defense against Mycobacterium tuberculosis has been suggested through epidemiological and in vitro studies; however, the mechanism is unclear. In this study, we demonstrate that vitamin A-triggered antimicrobial activity against M. tuberculosis requires expression of NPC2. Comparison of monocytes stimulated with all-trans retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D3), the biologically active forms of vitamin A and vitamin D, respectively, indicates that ATRA and 1,25D3 induce mechanistically distinct antimicrobial activities. Stimulation of primary human monocytes with ATRA did not result in expression of the antimicrobial peptide cathelicidin, which is required for 1,25D3 antimicrobial activity. In contrast, ATRA triggered a reduction in the total cellular cholesterol concentration, whereas 1,25D3 did not. Blocking ATRA-induced cellular cholesterol reduction inhibits antimicrobial activity as well. Bioinformatic analysis of ATRA- and 1,25D3-induced gene profiles suggests that NPC2 is a key gene in ATRA-induced cholesterol regulation. Knockdown experiments demonstrate that ATRA-mediated decrease in total cellular cholesterol content and increase in lysosomal acidification are both dependent upon expression of NPC2. Expression of NPC2 was lower in caseous tuberculosis granulomas and M. tuberculosis-infected monocytes compared with normal lung and uninfected cells, respectively. Loss of NPC2 expression ablated ATRA-induced antimicrobial activity. Taken together, these results suggest that the vitamin A-mediated antimicrobial mechanism against M. tuberculosis requires NPC2-dependent expression and function, indicating a key role for cellular cholesterol regulation in the innate immune response.
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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.