ArticleThe Journal of biological chemistry2021
Cholesterol and sphingomyelin are critical for Fcγ receptor-mediated phagocytosis of Cryptococcus neoformans by macrophages.
Article in The Journal of biological chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- The membrane distal domain of CD16a allosterically regulates NK cell ADCC.bioRxiv : the preprint server for biology · 2026Article
- Transcriptomic and lipidomic analysis of the cryptococcal lung granuloma reveals macrophage boundary programs and sphingolipid remodeling.Nature communications · 2026Article
- Time-resolved multi-omics reveals macrophage-centered immunometabolic remodeling in cutaneous dematiaceous fungal infection.Frontiers in immunology · 2026Article
- The lipid-podocyte axis: emerging clues in membranous nephropathy pathogenesis.Frontiers in medicine · 2026Review
- Article
- Extracellular Vesicles From Fungal Infection in Humans: A Key Player in Immunological Responses.Journal of extracellular biology · 2025Article
- CAR-macrophages targets CD26 to eliminate chronic myeloid leukemia stem cells.Experimental hematology & oncology · 2025Article
- Cryptococcal infection: host immunity, immune evasion and emerging immunotherapeutic strategies.Frontiers in cellular and infection microbiology · 2025Review
- Optical control of sphingolipid biosynthesis using photoswitchable sphingosines.Journal of lipid research · 2025Article
- Optical control of sphingolipid biosynthesis using photoswitchable sphingosines.bioRxiv : the preprint server for biology · 2024Article
- Biochemical Pathways Delivering Distinct Glycosphingolipid Patterns in MDA-MB-231 and MCF-7 Breast Cancer Cells.Current issues in molecular biology · 2024Review
- Lipid-driven interleaflet coupling of plasma membrane order regulates FcεRI signaling in mast cells.Biophysical journal · 2024Article
- Proton pump inhibitors enhance macropinocytosis-mediated extracellular vesicle endocytosis by inducing membrane v-ATPase assembly.Journal of extracellular vesicles · 2024Article
- Collaboration between a cis-interacting natural killer cell receptor and membrane sphingolipid is critical for the phagocyte function.Frontiers in immunology · 2024Article
- 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
- Extent of raft composition in a model plasma membrane.Biophysical journal · 2023Article
- Structural diversity of photoswitchable sphingolipids for optodynamic control of lipid microdomains.Biophysical journal · 2023Article
- A Fun-Guide to Innate Immune Responses to Fungal Infections.Journal of fungi (Basel, Switzerland) · 2022Review
- Vaccine protection by Cryptococcus neoformans Δsgl1 is mediated by γδ T cells via TLR2 signaling.Mucosal immunology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Cryptococcus neoformans is a fungal pathogen that causes life-threatening meningoencephalitis in lymphopenic patients. Pulmonary macrophages comprise the first line of host defense upon inhalation of fungal spores by aiding in clearance but can also potentially serve as a niche for their dissemination. Given that macrophages play a key role in the outcome of a cryptococcal infection, it is crucial to understand factors that mediate phagocytosis of C. neoformans. Since lipid rafts (high-order plasma membrane domains enriched in cholesterol and sphingomyelin [SM]) have been implicated in facilitating phagocytosis, we evaluated whether these ordered domains govern macrophages' ability to phagocytose C. neoformans. We found that cholesterol or SM depletion resulted in significantly deficient immunoglobulin G (IgG)-mediated phagocytosis of fungus. Moreover, repletion of macrophage cells with a raft-promoting sterol (7-dehydrocholesterol) rescued this phagocytic deficiency, whereas a raft-inhibiting sterol (coprostanol) significantly decreased IgG-mediated phagocytosis of C. neoformans. Using a photoswitchable SM (AzoSM), we observed that the raft-promoting conformation (trans-AzoSM) resulted in efficient phagocytosis, whereas the raft-inhibiting conformation (cis-AzoSM) significantly but reversibly blunted phagocytosis. We observed that the effect on phagocytosis may be facilitated by Fcγ receptor (FcγR) function, whereby IgG immune complexes crosslink to FcγRIII, resulting in tyrosine phosphorylation of FcR γ-subunit (FcRγ), an important accessory protein in the FcγR signaling cascade. Correspondingly, cholesterol or SM depletion resulted in decreased FcRγ phosphorylation. Repletion with 7-dehydrocholesterol restored phosphorylation, whereas repletion with coprostanol showed FcRγ phosphorylation comparable to unstimulated cells. Together, these data suggest that lipid rafts are critical for facilitating FcγRIII-mediated phagocytosis of C. neoformans.
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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 Socratic graph.