Candidalysin Induces Inflammatory Responses in the Human Microglial Cell Line HMC3 through Autophagy-Dependent Activation of Nuclear Factor-KappaB Signaling

• Material Type: 記事
• Title: Candidalysin Induces Inflammatory Responses in the Human Microglial Cell Line HMC3 through Autophagy-Dependent Activation of Nuclear Factor-KappaB Signaling
• Author Heading: Nonaka Saori; Katsuta Yui; Yamada Mana; Kanetsuki Shiori; Higashino Sana; Okayama Rikako; Hama Shiori; Nagaosa Kaz; Nakanishi Hiroshi; Shiratsuchi Akiko
• Publication Date: 2025
• Publication Date (W3CDTF): 2025
• Periodical title: BPB Reports
• No. or year of volume/issue: 8 6
• Volume: 8
• Issue: 6
• Pages: 227-233
• Publication date of volume/issue (W3CDTF): 2025
• Publication (Periodical Title): The Pharmaceutical Society of Japan
• Text Language Code: en
• Subject Heading: candidalysin; microglia; autophagy; nuclear factor-kappaB; neuroinflammation
• Target Audience: 一般
• DOI: 10.1248/bpbreports.8.6_227; https://doi.org/10.1248/bpbreports.8.6_227
• Related Material (URI): https://www.jstage.jst.go.jp/article/bpbreports/8/6/8_227/_pdf
• References: Epidemiology of Candida species infections in critically ill non-immunosuppressed patients; https://cir.nii.ac.jp/crid/1360011145874520704; Neurodegeneration and Inflammation—An Interesting Interplay in Parkinson’s Disease; https://cir.nii.ac.jp/crid/1360020701022970624; “Repair Me if You Can”: Membrane Damage, Response, and Control from the Viral Perspective; https://cir.nii.ac.jp/crid/1360022499888638976; Hidden Killers: Human Fungal Infections; https://cir.nii.ac.jp/crid/1360292619596445568; Microglia in neurodegeneration; https://cir.nii.ac.jp/crid/1360292620677644032; Microglia and amyloid precursor protein coordinate control of transient Candida cerebritis with memory deficits; https://cir.nii.ac.jp/crid/1360306911708972288; Neuroinflammation pathways: a general review; https://cir.nii.ac.jp/crid/1360574094372381312; Interaction between genetic factors, <i>Porphyromonas gingivalis</i> and microglia to promote Alzheimer’s disease; https://cir.nii.ac.jp/crid/1360580237142586112; <i>Porphyromonas gingivalis</i> and the pathogenesis of Alzheimer’s disease; https://cir.nii.ac.jp/crid/1360584343268355328; Innate Immune and Fungal Model of Alzheimer’s Disease; https://cir.nii.ac.jp/crid/1360588383735225472; Membrane protective role of autophagic machinery during infection of epithelial cells by <i>Candida albicans</i>; https://cir.nii.ac.jp/crid/1360588384957054592; Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis; https://cir.nii.ac.jp/crid/1360588389196450432; In Vitro Biophysical Characterization of Candidalysin: A Fungal Peptide Toxin; https://cir.nii.ac.jp/crid/1360588389340957696; Different Brain Regions are Infected with Fungi in Alzheimer’s Disease; https://cir.nii.ac.jp/crid/1360845539171506304; The NF- B Family of Transcription Factors and Its Regulation; https://cir.nii.ac.jp/crid/1360855569066544896; Development and regulation of single- and multi-species Candida albicans biofilms; https://cir.nii.ac.jp/crid/1360855569816935808; LC3 and Autophagy; https://cir.nii.ac.jp/crid/1361137046261931904; Candidalysin: discovery and function in Candida albicans infections; https://cir.nii.ac.jp/crid/1361699993897062912; Microglia-mediated neuroinflammation in neurodegenerative diseases; https://cir.nii.ac.jp/crid/1363107368815264768; Autophagy enhances NFκB activity in specific tissue macrophages by sequestering A20 to boost antifungal immunity; https://cir.nii.ac.jp/crid/1363107368896385792; The nuclear factor- B-interleukin-6 signalling pathway mediating vascular inflammation; https://cir.nii.ac.jp/crid/1363670319647848960; Autophagy is required for the activation of NFκB; https://cir.nii.ac.jp/crid/1363670321011058816
• Data Provider (Database): 国立情報学研究所 : CiNii Research; https://cir.nii.ac.jp/
• Original Data Provider (Database): Japan Link Center; https://japanlinkcenter.org/top; Crossref; https://www.crossref.org

• Summary, etc.: <p>Neuroinflammation induced by microglial activation has recently attracted attention as a cause of neurodegenerative diseases, such as Alzheimer’s disease (AD). <i>Candida albicans</i> is a prevalent fungal species in human microbiota, and suspected of causing AD through neuroinflammation, as <i>C. albicans</i> has been detected in the brain tissue of AD patients, and the intravenous injection of <i>C. albicans</i> induced mild memory impairment, accompanied by <i>C. albicans</i> invasion of the brain and neuroinflammation in mice. However, the detailed mechanism by which <i>C. albicans</i> induces neuroinflammation remains unclear. In this study, we showed that candidalysin, a cytolytic peptide toxin secreted by <i>C. albicans</i>, induces the production of the inflammatory cytokine IL-6 accompanied by nuclear translocation of nuclear factor-kappaB (NF-κB) through the degradation of inhibitor of κBα (IκBα) in the human microglial cell line HMC3. We also found that candidalysin induced autophagy, and that an autophagy inhibitor suppressed candidalysin-induced IκBα degradation, nuclear translocation of NF-κB, and IL-6 mRNA expression. These findings suggest that candidalysin triggers autophagy, which induces inflammatory responses via NF-κB in human microglia. Thus, the present study may have uncovered an important pathway for neuroinflammation via microglia when <i>C. albicans</i> invades the brain.</p>
• DOI: 10.1248/bpbreports.8.6_227
• Access Restrictions: インターネット公開
• Data Provider (Database): 科学技術振興機構 : J-STAGE; http://www.jstage.jst.go.jp