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

• DOI: 10.1016/j.celrep.2023.113240
• Publication Date: 2023-10-17T09:29:41Z
• Authors: 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. Richa...; Bernhard Hube; Julian R. Naglik; David B. Corry
• Keywords: 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)

The fungal pathogen Candida albicans is linked to chronic brain diseases such as Alzheimer's disease (AD), but the molecular basis of anti-Candida immunity remains unknown. We show that C. enters mouse from blood and induces two neuroimmune sensing mechanisms involving secreted aspartic proteinases (Saps) candidalysin. Saps disrupt tight junction proteins blood-brain barrier (BBB) permit invasion. also hydrolyze amyloid precursor protein (APP) into β (Aβ)-like peptides bind Toll-like receptor 4 (TLR4) promote killing in vitro while candidalysin engages integrin CD11b (Mac-1) on microglia. Recognition Aβ-like promotes clearance brain, disruption recognition through markedly prolongs cerebral mycosis. Thus, cleared innate immune Saps, Aβ, candidalysin, CD11b.