ArticleEMBO molecular medicine2015
Phagocytosis-dependent activation of a TLR9-BTK-calcineurin-NFAT pathway co-ordinates innate immunity to Aspergillus fumigatus.
Article in EMBO molecular medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
What it found
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The trial behind it
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Who cites it
113 citing papers in PubMed, 176 citations in OpenAlex.
- Trial
- Safety profiles of calcineurin inhibitor-related infections in the pediatric population: a real-world pharmacovigilance analysis.European journal of pediatrics · 2026Article
- The NFAT5-AR Axis Is Associated with Hyperosmolarity, Renal Dysfunction, and Neutrophil-Related Inflammatory Markers in Diabetic Retinopathy.International journal of molecular sciences · 2026Article
- Mycobacterial lipoarabinomannan negatively interferes with macrophage responses to Aspergillus fumigatus in-vitro.PloS one · 2026Article
- STAT1 drives M1 macrophage polarization during Aspergillus fumigatus infection.European journal of medical research · 2025Article
- Extensive diversity of unusual microorganisms associated with severe pneumonia in kidney transplant recipients.PLoS pathogens · 2025Article
- An IFN/STAT1/CYBB axis defines protective plasmacytoid DC-neutrophil crosstalk in Aspergillus fumigatus-infected mice.The Journal of clinical investigation · 2025Article
- Enhanced virulence and stress tolerance are signatures of epidemiologically successful Shigella sonnei.Nature communications · 2025Article
- Nocardiosis in a Patient with Nephrotic Syndrome Treated with Glucocorticoids and Tacrolimus.Internal medicine (Tokyo, Japan) · 2025Article
- Cytosolic nucleic acid sensing as driver of critical illness: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2025Review
- Article
- Increased NFAT and NFκB signalling contribute to the hyperinflammatory phenotype in response to Aspergillus fumigatus in a mouse model of cystic fibrosis.PLoS pathogens · 2025Article
- NFATc1 in CD4The journal of allergy and clinical immunology. Global · 2025Article
- Conditional requirement for dimerization of the membrane-binding module for BTK signaling in lymphocyte cell lines.Science signaling · 2025Article
- Calcineurin inhibition enhanceseLife · 2024Article
- Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities.Nature microbiology · 2024Review
- BTK inhibitor-induced defects in human neutrophil effector activity against Aspergillus fumigatus are restored by TNF-α.JCI insight · 2024Article
- Severe infections requiring intensive care unit admission in patients receiving ibrutinib for hematological malignancies: a groupe de recherche respiratoire en réanimation onco-hématologique (GRRR-OH) study.Annals of intensive care · 2023Article
- New anticancer therapeutics impact fungal pathobiology, infection dynamics, and outcome.PLoS pathogens · 2023Article
- Immune responses to human fungal pathogens and therapeutic prospects.Nature reviews. Immunology · 2023Review
53 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Transplant recipients on calcineurin inhibitors are at high risk of invasive fungal infection. Understanding how calcineurin inhibitors impair fungal immunity is a key priority for defining risk of infection. Here, we show that the calcineurin inhibitor tacrolimus impairs clearance of the major mould pathogen Aspergillus fumigatus from the airway, by inhibiting macrophage inflammatory responses. This leads to defective early neutrophil recruitment and fungal clearance. We confirm these findings in zebrafish, showing an evolutionarily conserved role for calcineurin signalling in neutrophil recruitment during inflammation. We find that calcineurin-NFAT activation is phagocytosis dependent and collaborates with NF-κB for TNF-α production. For yeast zymosan particles, activation of macrophage calcineurin-NFAT occurs via the phagocytic Dectin-1-spleen tyrosine kinase pathway, but for A. fumigatus, activation occurs via a phagosomal TLR9-dependent and Bruton's tyrosine kinase-dependent signalling pathway that is independent of MyD88. We confirm the collaboration between NFAT and NF-κB for TNF-α production in primary alveolar macrophages. These observations identify inhibition of a newly discovered macrophage TLR9-BTK-calcineurin-NFAT signalling pathway as a key immune defect that leads to organ transplant-related invasive aspergillosis.
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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.