小胶质细胞上表达的 Toll 样受体 4 和 CD11b 协调清除白色念珠菌大脑真菌感染。
Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis.
机构信息
Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA; Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
出版信息
Cell Rep. 2023 Oct 31;42(10):113240. doi: 10.1016/j.celrep.2023.113240. Epub 2023 Oct 17.
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.
真菌病原体白色念珠菌与慢性脑部疾病（如阿尔茨海默病，AD）有关，但脑内抗真菌免疫的分子基础仍不清楚。我们发现白色念珠菌从血液进入小鼠大脑，并诱导两种涉及分泌天冬氨酸蛋白酶（Saps）和念珠菌溶素的神经免疫感应机制。Saps 破坏血脑屏障（BBB）的紧密连接蛋白，从而允许真菌入侵大脑。Saps 还将淀粉样前体蛋白（APP）水解为类似淀粉样β（Aβ）的肽，这些肽与 Toll 样受体 4（TLR4）结合，并促进真菌在体外的杀伤，而念珠菌溶素则与小胶质细胞上的整合素 CD11b（Mac-1）结合。对 Aβ样肽和念珠菌溶素的识别可促进真菌从大脑中清除，而通过 CD11b 破坏念珠菌溶素的识别则可显著延长白色念珠菌的大脑真菌感染。因此，白色念珠菌通过涉及 Saps、Aβ、念珠菌溶素和 CD11b 的先天免疫机制从大脑中清除。
Zotero 插件