Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis
Medical Sciences
Amyloid beta-Peptides
CD11b Antigen
QH301-705.5
Medical Immunology
610
Diseases
CP: Immunology
Article
3. Good health
Fungal Proteins
Toll-Like Receptor 4
Mice
Immune System Diseases
Mycoses
Alzheimer Disease
Allergy and Immunology
CP: Neuroscience
616
Candida albicans
Medical Specialties
Medicine and Health Sciences
Animals
Microglia
Biology (General)
DOI:
10.1016/j.celrep.2023.113240
Publication Date:
2023-10-17T09:29:41Z
AUTHORS (20)
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.
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CITATIONS (23)
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