Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.

Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.
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DOI:
10.3389/fimmu.2022.804674
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发表时间:
2022
影响因子:
7.3
通讯作者:
Drummond, Rebecca A. A.
Drummond, Rebecca A. A.
中科院分区:
医学2区
文献类型:
--
作者:
Mohamed, Sally H. H.;Nyazika, Tinashe K. K.;Ssebambulidde, Kenneth;Lionakis, Michail S. S.;Meya, David B. B.;Drummond, Rebecca A. A.

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隐球菌性脑膜炎 (CM) 是人类中枢神经系统 (CNS) 真菌感染的主要原因,大多数病例来自非洲大陆。部分原因是该地区艾滋病毒感染负担沉重,并且获得标准护理(包括最佳消毒抗真菌药物治疗)的机会减少。因此,CM 占所有 HIV 相关死亡率的 10-15%,其中很大一部分是可以预防的。对 CM 病原体——新型隐球菌的免疫力目前还只是部分了解。骨髓细胞(尤其是巨噬细胞)的激活需要产生 IFNγ 的 CD4+ T 细胞,以实现真菌杀灭和清除。然而,巨噬细胞也可能充当真菌酵母细胞的储存库,保护它们免受宿主免疫检测,从而促进潜在感染或持续性慢性炎症。在本章中,我们回顾了非洲 CNS 真菌感染的流行病学和发病机制,重点关注 CM 以及用于预防新型隐球菌感染的抗真菌免疫途径。我们还强调了需要优先考虑的研究和政策领域,以帮助减轻非洲中枢神经系统真菌病的负担。
Cryptococcal meningitis (CM) is the leading cause of central nervous system (CNS) fungal infections in humans, with the majority of cases reported from the African continent. This is partly due to the high burden of HIV infection in the region and reduced access to standard-of-care including optimal sterilising antifungal drug treatments. As such, CM is responsible for 10-15% of all HIV-related mortality, with a large proportion being preventable. Immunity to the causative agent of CM, Cryptococcus neoformans, is only partially understood. IFNγ producing CD4+ T-cells are required for the activation of myeloid cells, especially macrophages, to enable fungal killing and clearance. However, macrophages may also act as a reservoir of the fungal yeast cells, shielding them from host immune detection thus promoting latent infection or persistent chronic inflammation. In this chapter, we review the epidemiology and pathogenesis of CNS fungal infections in Africa, with a major focus on CM, and the antifungal immune pathways operating to protect against C. neoformans infection. We also highlight the areas of research and policy that require prioritisation to help reduce the burden of CNS fungal diseases in Africa.
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