ArticleThe Journal of clinical investigation2020
FTY720 reactivates cryptococcal granulomas in mice through S1P receptor 3 on macrophages.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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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.
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
28 citing papers in PubMed, 36 citations in OpenAlex.
- Fungal Infections Associated with Sphingosine 1-Phosphate Receptor Modulators: Immunological Mechanisms, Clinical Patterns, and Management Considerations.Microorganisms · 2026Review
- Immunological mechanism behind reactivated cryptococcosis in persistently infected mice following FTY720 treatment.Infection and immunity · 2026Article
- Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.Nature communications · 2026Article
- Alternatively activated monocyte-derived myeloid cells promote extracellular pathogen persistence in pulmonary fungal granulomas.The Journal of experimental medicine · 2026Article
- Viral Infection and the Blood-Brain Barrier: Molecular Research Insights and Therapies.The Journal of infectious diseases · 2025Review
- Dormant yet dangerous: the role of cell rest in perseverance.Future microbiology · 2025Review
- Cryptococcus: Emerging host risk factors for infection.PLoS pathogens · 2025Article
- The pathobiology of human fungal infections.Nature reviews. Microbiology · 2024Review
- Inbred Mouse Models inJournal of fungi (Basel, Switzerland) · 2024Review
- Histoplasmosis in a fingolimod-treated patient: case report and scoping review.Revista do Instituto de Medicina Tropical de Sao Paulo · 2024Article
- Kicking sleepers out of bed: Macrophages promote reactivation of dormant Cryptococcus neoformans by extracellular vesicle release and non-lytic exocytosis.PLoS pathogens · 2023Article
- The biological functions of sphingolipids in plant pathogenic fungi.PLoS pathogens · 2023Review
- Role of sphingolipids in the host-pathogen interaction.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2023Article
- Immune responses to human fungal pathogens and therapeutic prospects.Nature reviews. Immunology · 2023Review
- Mouse Model of Latent Cryptococcal Infection and Reactivation.Methods in molecular biology (Clifton, N.J.) · 2023Article
- An Immunogenic and Slow-Growing Cryptococcal Strain Induces a Chronic Granulomatous Infection in Murine Lungs.Infection and immunity · 2022Article
- Vaccine protection by Cryptococcus neoformans Δsgl1 is mediated by γδ T cells via TLR2 signaling.Mucosal immunology · 2022Article
- Cryptococcal Meningitis Reported With Fingolimod Treatment: Case Series.Neurology(R) neuroimmunology & neuroinflammation · 2022Article
- Molecular Pharmacology and Novel Potential Therapeutic Applications of Fingolimod.Frontiers in pharmacology · 2022Review
- Three Models of Vaccination Strategies Against Cryptococcosis in Immunocompromised Hosts Using Heat-KilledFrontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
FTY720 is a treatment for relapsing remitting multiple sclerosis (MS). It is an analog of sphingosine-1-phosphate (S1P) and targets S1P receptors 1, 3, 4, and 5. Recent reports indicate an association between long-term exposure to FTY720 and cases of cryptococcal infection. Here, we studied the effect of FTY720 and its derivative, BAF312, which only target S1P receptors 1 and 5, in a mouse model of cryptococcal infection. We found that treatment with FTY720, but not with BAF312, led to decreased survival and increased organ burden in mouse cryptococcal granulomas. Both FTY720 and BAF312 caused a profound CD4+ and CD8+ T cell depletion in blood and lungs but only treatment with FTY720 led to cryptococcal reactivation. Treatment with FTY720, but not with BAF312, was associated with disorganization of macrophages and with M2 polarization at the granuloma site. In a cell system, FTY720 decreased phagocytosis and production of reactive oxygen species by macrophages, a phenotype recapitulated in the S1pr3-/- knockout macrophages. Our results suggest that FTY720 reactivates cryptococcosis from the granuloma through a S1P receptor 3-mediated mechanism and support the rationale for development of more-specific receptor modulators for therapeutic use of MS.
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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.