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Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis
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SYSNO ASEP 0578936 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis Author(s) Wu, Y. (US)
Du, S. (US)
Bimler, Lynn H. (US)
Mauk, K. E. (US)
Lortal, L. (GB)
Kichik, N. (GB)
Griffiths, J. S. (GB)
Osička, Radim (MBU-M) RID, ORCID
Song, L. (US)
Polsky, K. (US)
Kasper, L. (DE)
Šebo, Peter (MBU-M) RID, ORCID
Weatherhead, J. (US)
Knight, J. M. (US)
Kheradmand, F. (US)
Zheng, H. (US)
Richardson, J. P. (GB)
Hube, B. (DE)
Naglik, J. R. (GB)
Corry, D. B. (US)Article number 113240 Source Title Cell Reports. - : Cell Press - ISSN 2211-1247
Roč. 42, č. 10 (2023)Number of pages 19 s. Language eng - English Country US - United States Keywords secreted aspartic proteinases ; central-nervous-system ; allergic responses ; fungal-infection ; brain ; tissue ; identification ; recognition ; astrocytes ; generation OECD category Microbiology Method of publishing Open access Institutional support MBU-M - RVO:61388971 UT WOS 001096956400001 EID SCOPUS 85173344141 DOI 10.1016/j.celrep.2023.113240 Annotation 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 as-partic 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 D (AD)-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 AD-like peptides and candidalysin pro-motes 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, AD, candidalysin, and CD11b. Workplace Institute of Microbiology Contact Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Year of Publishing 2024 Electronic address https://www.sciencedirect.com/science/article/pii/S2211124723012524?via%3Dihub
Number of the records: 1