Rhizopus arrhizus.
Rhizopus arrhizus.
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无根根霉。
DOI：
10.1016/j.tim.2023.03.013
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发表时间：
2023
影响因子：
15.9
通讯作者：
Corzo-León DE
中科院分区：
文献类型：
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作者：
Corzo-León DE
葡萄糖调节蛋白78 （GRP78）是野根霉在鼻内皮细胞和鼻上皮细胞上的主要受体。高葡萄糖、铁超载或酸性环境会增加GRP78的表达，增加真菌的结合和摄取。这些情况发生在高血糖状态，如急性糖尿病酮症酸中毒或慢性不受控制的糖尿病。内皮细胞和鼻上皮细胞中GRP78的高表达可以解释主要见于糖尿病患者的鼻-眶-脑毛霉菌病的表现。然而，在肺泡上皮细胞中，arrhizus胚结合的是一个3 - β1整合素异源二聚体而不是GRP78，并且3 - β1整合素被认为是肺粘膜的特异性受体。此外，β1整合素信号传导触发表皮生长因子受体（EGFR）的激活，允许肺泡细胞内吞和随后的细胞损伤。主要的毛霉病原体相关分子模式（PAMPs）是孢子外壳蛋白同源物（CotH），它赋予了入侵宿主细胞的能力（入侵因子）。arrhizus芽孢中的CotH3是GRP78的真菌配体，而CotH7是肺泡细胞中<s:1> 3β1整合素的细胞表面配体。受体的不同解剖分布及其相应的真菌表位已经被提出来解释血液病恶性肿瘤患者和糖尿病患者之间临床综合征的差异。
The glucose-regulated protein 78 (GRP78) is the main human receptor for R. arrhizus on endothelial and nasal epithelial cells. High glucose, iron overload, or acidotic environments increase GRP78 expression, increasing fungal binding and uptake. These conditions are found during hyperglycaemic conditions such as acute diabetic ketoacidosis or chronic uncontrolled diabetes. Highly expressed GRP78 in endothelial and nasal epithelial cells would explain the presentation as rhino-orbital-cerebral mucormycosis seen mainly in individuals with diabetes. However, in alveolar epithelial cells, R. arrhizus germlings bind to an⍺ 3β1 integrin heterodimer instead of GRP78, and⍺ 3β1 integrin is considered the specific receptor for Mucorales in the lung. Further, β1 integrin signalling triggers the activation of the epidermal growth factor receptor (EGFR), allowing endocytosis of germlings by alveolar cells and subsequent cell damage.The main Mucorales Pathogen Associated Molecular Patterns (PAMPs) are the spore coat protein homologues (CotH), which confer the ability to invade host cells (invasins). CotH3 in R. arrhizus germlings is the fungal ligand for GRP78, while CotH7 is the cell surface ligand for⍺ 3β1 integrin in alveolar cells. The different anatomic distribution of receptors and their corresponding fungal epitopes has been proposed to explain the differences in clinical syndromes seen between individuals living with haematological malignancies and individuals with diabetes.