Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis

Yifan Wu; Shuqi Du; Lynn H. Bimler; Kelsey E. Mauk; Léa Lortal; Nessim Kichik; James S. Griffiths; Radim Osicka; Lizhen Song; Katherine Polsky; Lydia Kasper; Peter Sebo; Jill Weatherhead; J. Morgan Knight; Farrah Kheradmand; Hui Zheng; Jonathan P. Richardson; Bernhard Hube; Julian R. Naglik; David B. Corry

Cell Reports (Oct 2023)

Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis

Yifan Wu,
Shuqi Du,
Lynn H. Bimler,
Kelsey E. Mauk,
Léa Lortal,
Nessim Kichik,
James S. Griffiths,
Radim Osicka,
Lizhen Song,
Katherine Polsky,
Lydia Kasper,
Peter Sebo,
Jill Weatherhead,
J. Morgan Knight,
Farrah Kheradmand,
Hui Zheng,
Jonathan P. Richardson,
Bernhard Hube,
Julian R. Naglik,
David B. Corry

Affiliations

Yifan Wu: Department 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 Du: Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Lynn H. Bimler: Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Kelsey E. Mauk: Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Léa Lortal: Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 1UL, UK
Nessim Kichik: Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 1UL, UK
James S. Griffiths: Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 1UL, UK
Radim Osicka: Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Lizhen Song: Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Katherine Polsky: Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Lydia Kasper: Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans Knoell Institute Jena (HKI), 07737 Jena, Germany
Peter Sebo: Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
Jill Weatherhead: Department 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 Knight: Departments of Pathology & Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Farrah Kheradmand: Department 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 Zheng: Department 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. Richardson: Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 1UL, UK
Bernhard Hube: Department 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; Corresponding author
Julian R. Naglik: Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College London, London SE1 1UL, UK; Corresponding author
David B. Corry: Department 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; Corresponding author

Journal volume & issue: Vol. 42, no. 10
p. 113240

Abstract

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Summary: 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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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