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

0578936 - MBÚ 2024 RIV US eng J - Journal Article
Wu, Y. - Du, S. - Bimler, Lynn H. - Mauk, K. E. - Lortal, L. - Kichik, N. - Griffiths, J. S. - Osička, Radim - Song, L. - Polsky, K. - Kasper, L. - Šebo, Peter - Weatherhead, J. - Knight, J. M. - Kheradmand, F. - Zheng, H. - Richardson, J. P. - Hube, B. - Naglik, J. R. - Corry, D. B.
Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis.
Cell Reports. Roč. 42, č. 10 (2023), č. článku 113240. ISSN 2211-1247. E-ISSN 2211-1247
Institutional support: RVO:61388971
Keywords : secreted aspartic proteinases * central-nervous-system * allergic responses * fungal-infection * brain * tissue * identification * recognition * astrocytes * generation
OECD category: Microbiology
Impact factor: 8.8, year: 2022
Method of publishing: Open access
https://www.sciencedirect.com/science/article/pii/S2211124723012524?via%3Dihub

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.
Permanent Link: https://hdl.handle.net/11104/0347845