Department of Anatomical Sciences, Liberty University College of Osteopathic Medicine, Lynchburg, VA, United States.
Department of Biology and Chemistry, Liberty University, Lynchburg, VA, United States.
Front Cell Infect Microbiol. 2022 Mar 17;12:861405. doi: 10.3389/fcimb.2022.861405. eCollection 2022.
is a ubiquitous opportunistic fungal pathogen typically causing disease in immunocompromised individuals and is globally responsible for about 15% of AIDS-related deaths annually first causes pulmonary infection in the host and then disseminates to the brain, causing meningoencephalitis. The yeast must obtain and metabolize carbon within the host in order to survive in the central nervous system and cause disease. Communication between pathogen and host involves recognition of multiple carbon-containing compounds on the yeast surface: polysaccharide capsule, fungal cell wall, and glycosylated proteins comprising the major immune modulators. The structure and function of polysaccharide capsule has been studied for the past 70 years, emphasizing its role in virulence. While protected by the capsule, fungal cell wall has likewise been a focus of study for several decades for its role in cell integrity and host recognition. Associated with both of these major structures are glycosylated proteins, which exhibit known immunomodulatory effects. While many studies have investigated the role of carbon metabolism on virulence and survival within the host, the precise mechanism(s) affecting host-pathogen communication remain ill-defined. This review summarizes the current knowledge on mutants in carbon metabolism and their effect on the host immune response that leads to changes in pathogen recognition and virulence. Understanding these critical interactions will provide fresh perspectives on potential treatments and the natural history of cryptococcal disease.
隐球菌是一种普遍存在的机会性真菌病原体，通常在免疫功能低下的个体中引起疾病，每年约有全球 15%的艾滋病相关死亡与它有关。它首先在宿主中引起肺部感染，然后传播到大脑，引起脑膜脑炎。酵母必须在宿主内获取和代谢碳，才能在中枢神经系统中存活并引起疾病。病原体和宿主之间的通信涉及到对酵母表面上多种含碳化合物的识别：多糖荚膜、真菌细胞壁和糖基化蛋白，它们构成了主要的免疫调节剂。多糖荚膜的结构和功能已经研究了 70 年，强调了它在毒力中的作用。虽然受到荚膜的保护，但真菌细胞壁几十年来一直是研究的焦点，因为它在细胞完整性和宿主识别中发挥作用。与这两种主要结构相关的是糖基化蛋白，它表现出已知的免疫调节作用。虽然许多研究都调查了碳代谢对宿主内毒力和生存的作用，但影响宿主-病原体通信的确切机制仍不清楚。本综述总结了碳代谢突变体及其对宿主免疫反应的影响的最新知识，这些影响导致了病原体识别和毒力的变化。了解这些关键相互作用将为潜在的治疗方法和隐球菌病的自然史提供新的视角。
