ArticleCell reports2023
Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis.
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Article in Cell reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 53 citations in OpenAlex.
- Delineating the Concerted Action of Virulence Attributes in Candida albicans Systemic Infection.Journal of cellular and molecular medicine · 2026Article
- The potential and therapeutic advances of the integrin family in neurological disorders.Neural regeneration research · 2026Article
- Microglia and neuroinflammation: An in-depth analysis from functional diversity to disease mechanisms.Clinical and translational medicine · 2026Review
- A mechanistic framework linking the oral microbiome to Alzheimer's disease through neuroinflammation.Journal of Alzheimer's disease : JAD · 2026Review
- Candidalysin InhibitsInternational journal of molecular sciences · 2026Article
- PVNJournal of neuroinflammation · 2026Article
- Phosphorylated tau exhibits antimicrobial activity capable of neutralizing herpes simplex virus 1 infectivity in human neurons.Nature neuroscience · 2026Article
- Use of a human immortalized microglia cell line to study recognition, phagocytosis, and intracellular survival ofmSphere · 2026Article
- Targeting the Gut Microbiota: Mechanistic Investigation of Polyphenol Modulation of the Gut-Brain Axis in Alzheimer's Disease.International journal of molecular sciences · 2026Review
- Fast Interneuron Dysfunction in Laminar Neural Mass Model Reproduces Alzheimer's Oscillatory Biomarkers.Human brain mapping · 2026Article
- Microbiome dynamics and early microbial signatures predict bone regeneration in marsupialized jaw lesions: a longitudinal 16S sequencing cohort study.Journal of oral microbiology · 2026Article
- Tight junction suppression by candidalysin promotes gut-to-blood dissemination ofFrontiers in microbiology · 2026Article
- Pathogens Association with Alzheimer Disease: Emerging Concepts and New Perspectives.Current gene therapy · 2026Review
- Melanin and Neuromelanin in Humans: Insights Across Health, Aging, Diseases, and Unexpected Aspects of Fungal Melanogenesis.Biomolecules · 2025Review
- The fungal peptide toxin candidalysin induces distinct membrane repair mechanisms compared to bacterial pore-forming toxins.Cell death discovery · 2025Article
- Exploring the intricate link between gut microbiota dysbiosis and the aging process: implications for age-related diseases.Gut pathogens · 2025Review
- Simple molecules make difference: short peptides play a novel role in slowing senescence.npj aging · 2025Review
- Neurodegeneration as Ecosystem Failure: A New Paradigm for Prevention and Treatment.International journal of molecular sciences · 2025Review
- Microbial links to Alzheimer's disease.PLoS pathogens · 2025Review
- Commensal colonization ofMicrobiology spectrum · 2025Article
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Authors and funding
20 authors at 5 institutions in 4 countries.
Yifan WuDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Shuqi DuDepartment of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Lynn H BimlerDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Kelsey E MaukDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Léa LortalCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 1UL, UK.
Nessim KichikCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 1UL, UK.
James S GriffithsCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 1UL, UK.
Radim OsickaInstitute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.
Lizhen SongDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Katherine PolskyDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Lydia KasperDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena (HKI), 07737 Jena, Germany.
Peter SeboInstitute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic.
Jill WeatherheadDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; National School of Tropical Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
J Morgan KnightDepartments of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Farrah KheradmandDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Departments of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston, TX 77030, USA.
Hui ZhengDepartment of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Huffington Center on Aging, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Jonathan P RichardsonCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 1UL, UK.
Bernhard HubeDepartment of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena (HKI), 07737 Jena, Germany; Institute of Microbiology, Friedrich Schiller University, 07737 Jena, Germany. Electronic address: bernhard.hube@hki-jena.de.
Julian R NaglikCentre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, London SE1 1UL, UK. Electronic address: julian.naglik@kcl.ac.uk.
David B CorryDepartment of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Departments of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Biology of Inflammation Center, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Michael E. DeBakey VA Center for Translational Research on Inflammatory Diseases, Houston, TX 77030, USA. Electronic address: dcorry@bcm.edu.
Baylor College of Medicine · USKing's College London · GBCzech Academy of Sciences · CZLeibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) · DEMichael E. DeBakey VA Medical Center · US
Funding
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MHost and Fungal Regulation of Type 17 Immunity to Oral CandidiasisR37DE022550 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Sarah L Gaffen · 2017 to 2026
$5.6MRESEARCH TRAINING IN LUNG DISEASET32HL007747 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI ROSAS, IVAN O. · 1993 to 2020
$5.1MImmunology Scientist Training ProgramT32AI053831 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI CORRY, DAVID B · 2003 to 2018
$4.2MPathogenesis of Polymicrobial Cerebritis-Related DementiaR01AI135803 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI CORRY, DAVID B, KHERADMAND, FARRAH · 2018 to 2022
$3.8MCollaborative Research Training in Thrombosis and InflammationT32HL139425 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Miguel Angel Cruz, ROLANDO E RUMBAUT · 2018 to 2026
$2.4MRole of Let-7 as genetic modifier of Alzheimer's DiseaseR01HL140398 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI CORRY, DAVID B, RODRIGUEZ, ANTONY · 2018 to 2022
$2.4MTh1 and Th17 Mediators in Experimental EmphysemaR01HL117181 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI CORRY, DAVID B, KHERADMAND, FARRAH · 2013 to 2016
$1.5MDiscovering the Immunologic Mechanism of Ascaris-induced Allergic Airway Disease.K08AI143968 · NIAID · BAYLOR COLLEGE OF MEDICINE · PI WEATHERHEAD, JILL ELIZABETH · 2020 to 2024
$911kDevelopment of Broad-Spectrum Cyclic Amphiphilic Peptides against Multidrug-Resistant BacteriaR41AI164997 · NIAID · AJK BIOPHARMACEUTICAL LLC · PI KAZEMINY, ASSAD, TIWARI, RAKESH K · 2022 to 2023
$597kBD Biosciences Special Order LSRIIS10RR024574 · NCRR · BAYLOR COLLEGE OF MEDICINE · PI LUMPKIN, ELLEN A · 2009 to 2009
$430kMolecular and Cellular Dissection of miRNAs in Controlling Allergic Airway Inflammation in MiceI01BX004828 · VA · MICHAEL E DEBAKEY VA MEDICAL CENTER · PI CORRY, DAVID B · 2020 to 2023
–BLRD VA I01 BX004828NCI NIH HHS P30 CA125123NCRR NIH HHS S10 RR024574NHLBI NIH HHS R01 HL117181NHLBI NIH HHS R01 HL140398NHLBI NIH HHS T32 HL007747NHLBI NIH HHS T32 HL139425NIAID NIH HHS K08 AI143968NIAID NIH HHS R01 AI135803NIAID NIH HHS R41 AI164997NIAID NIH HHS T32 AI053831NIDCR NIH HHS R37 DE022550Wellcome TrustWellcome Trust 214229_Z_18_Z
Abstract
The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of brain anti-Candida immunity remains unknown. We show that C. albicans enters the mouse brain from the blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) and candidalysin. Saps disrupt tight junction proteins of the blood-brain barrier (BBB) to permit fungal brain invasion. Saps also hydrolyze amyloid precursor protein (APP) into amyloid β (Aβ)-like peptides that bind to Toll-like receptor 4 (TLR4) and promote fungal killing in vitro while candidalysin engages the integrin CD11b (Mac-1) on microglia. Recognition of Aβ-like peptides and candidalysin promotes fungal clearance from the brain, and disruption of candidalysin recognition through CD11b markedly prolongs C. albicans cerebral mycosis. Thus, C. albicans is cleared from the brain through innate immune mechanisms involving Saps, Aβ, candidalysin, and CD11b.
Indexed as
CD11b AntigenMicrogliaMycosesToll-Like Receptor 4Alzheimer DiseaseAmyloid beta-PeptidesAnimalsCandida albicansFungal ProteinsMiceAmyloid beta-PeptidesCD11b AntigenFungal ProteinsToll-Like Receptor 4Alzheimer’s diseaseamyloid betablood-brain barrierCandida albicanscandidalysinCD11bcerebral mycosisCP: ImmunologyCP: Neurosciencemicrogliasecreted aspartic proteinaseToll-like Receptor 4
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