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星形胶质细胞相互作用:对真菌破坏血脑屏障、脑侵袭和脑膜炎进展的影响。

-astrocyte interactions: effect on fungal blood brain barrier disruption, brain invasion, and meningitis progression.

作者信息

Woo Yeon Hwa, Martinez Luis R

机构信息

Department of Metallurgical, Materials and Biomedical Engineering, College of Engineering, The University of Texas at El Paso, El Paso, TX, USA.

Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, FL, USA.

出版信息

Crit Rev Microbiol. 2021 Mar;47(2):206-223. doi: 10.1080/1040841X.2020.1869178. Epub 2021 Jan 21.

Abstract

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 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 . As astrocytes also make up the neurovascular unit at the blood-brain barrier (BBB), which 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 -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 BBB transmigration, brain invasion, colonization, and meningitis.

摘要

是一种机会性、嗜神经性且有荚膜的真菌,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的地区。该真菌的多糖荚膜是主要的致病因素,在感染期间大量释放,导致宿主出现免疫抑制缺陷。尽管在致命的CM中,荚膜物质通常与反应性星形胶质细胞有关,但关于星形胶质细胞与该真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了血脑屏障(BBB)处的神经血管单元,而该真菌必须穿过血脑屏障才能在中枢神经系统定植并引发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,星形胶质细胞与包括调节脑颅内压、免疫功能和水稳态在内的神经系统疾病有关。因此,在本综述中,我们提供了星形胶质细胞生物学的概述,并讨论了关于该真菌与星形胶质细胞相互作用的现有知识,包括它们在CM发展中的作用。这种以胶质细胞为中心的脑隐球菌病观点表明,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该真菌穿过血脑屏障、脑侵袭、定植和脑膜炎。

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