Abstract

Cryptococcus neoformans is an opportunistic, neurotropic, and encapsulated fungus that causes life-threatening cryptococcal meningitis (CM), especially in regions of the world where AIDS is endemic. The polysaccharide capsule of C. neoformans is the fungus major virulent factor, being copiously released during infection and causing immunosuppressive defects in the host. Although the capsular material is commonly associated with reactive astrocytes in fatal CM, little is known about the molecular and cellular interactions among astroglia and C. neoformans. As astrocytes also make up the neurovascular unit at the blood–brain barrier (BBB), which C. neoformans must transverse to colonize the central nervous system and cause CM; these cells may play a significant regulatory role in the prevention and progression of infection. For example, astrocytes are implicated in neurological disease including the regulation of cerebral intracranial pressure, immune function, and water homeostasis. Hence, in this review, we provide a general overview of astroglia biology and discuss the current knowledge on C. neoformans–astrocyte interactions including their involvement in the development of CM. This “gliocentric view” of cerebral cryptococcosis suggests that therapeutic interventions particularly targeting at preserving the neuroprotective function of astrocytes may be used in preventing and managing C. neoformans BBB transmigration, brain invasion, colonization, and meningitis.

摘要

新型隐球菌是一种机会性、嗜神经性和包裹性真菌，可导致危及生命的隐球菌性脑膜炎 (CM)，尤其是在艾滋病流行地区。新型隐球菌的多糖荚膜是真菌的主要毒力因子，在感染过程中大量释放，导致宿主免疫抑制缺陷。虽然荚膜材料通常与致命的 CM 中的反应性星形胶质细胞相关联，但对星形胶质细胞和新生念珠菌之间的分子和细胞相互作用知之甚少。由于星形胶质细胞也构成血脑屏障 (BBB) 处的神经血管单元，新生隐球菌必须横向定植中枢神经系统并引起 CM；这些细胞可能在感染的预防和进展中发挥重要的调节作用。例如，星形胶质细胞与神经系统疾病有关，包括调节脑颅内压、免疫功能和水分稳态。因此，在这篇综述中，我们提供了星形胶质细胞生物学的一般概述，并讨论了关于新型隐球菌- 星形胶质细胞相互作用的当前知识，包括它们参与 CM 的发展。脑隐球菌病的这种“以神经胶质为中心的观点”表明，特别针对保护星形胶质细胞神经保护功能的治疗干预措施可用于预防和管理新型隐球菌 BBB 轮回、脑侵袭、定植和脑膜炎。