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.

• Klíčová slova
• Alzheimer’s disease, CD11b, CP: Immunology, CP: Neuroscience, Candida albicans, Toll-like Receptor 4, amyloid beta, blood-brain barrier, candidalysin, cerebral mycosis, microglia, secreted aspartic proteinase,
• MeSH
• Alzheimerova nemoc metabolismus   mikrobiologie   MeSH
• amyloidní beta-protein metabolismus   MeSH
• antigeny CD11b * metabolismus   MeSH
• Candida albicans metabolismus   MeSH
• fungální proteiny metabolismus   MeSH
• mikroglie * metabolismus   mikrobiologie   MeSH
• mykózy * genetika   metabolismus   MeSH
• myši MeSH
• toll-like receptor 4 * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• amyloidní beta-protein MeSH
• antigeny CD11b * MeSH
• fungální proteiny MeSH
• toll-like receptor 4 * MeSH