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首页> 外文期刊>Infection and immunity >Candida albicans β-Glucan Exposure Is Controlled by the Fungal CEK1-Mediated Mitogen-Activated Protein Kinase Pathway That Modulates Immune Responses Triggered through Dectin-1
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Candida albicans β-Glucan Exposure Is Controlled by the Fungal CEK1-Mediated Mitogen-Activated Protein Kinase Pathway That Modulates Immune Responses Triggered through Dectin-1

机译：白色念珠菌β-葡聚糖的暴露受真菌CEK1介导的丝裂原活化蛋白激酶途径的调节，该途径调节由Dectin-1触发的免疫反应。

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Innate immunity to Candida albicans depends upon the recognition of molecular patterns on the fungal cell wall. However, the masking of major components such as β-glucan seems to be a mechanism that fungi have evolved to avoid immune cell recognition through the dectin-1 receptor. Although the role of C. albicans mitogen-activated protein kinase (MAPK) pathways as virulence determinants has been established previously with animal models, the mechanism involved in this behavior is largely unknown. In this study we demonstrate that a disruption of the C. albicans extracellular signal-regulated kinase (ERK)-like 1 (CEK1)-mediated MAPK pathway causes enhanced cell wall β-glucan exposure, triggering immune responses more efficiently than the wild type, as measured by dectin-1-mediated specific binding and human dendritic cell (hDC)- and macrophage-mediated phagocytosis, killing, and activation of intracellular signaling pathways. At the molecular level, the disruption of CEK1 resulted in altered spleen tyrosine kinase (Syk), Raf-1, and ERK1/2 activations together with IκB degradation on hDCs and increased dectin-1-dependent activator protein 1 (AP-1) activation on transfected cells. In addition, concurring with these altered pathways, we detected increased reactive oxygen species production and cytokine secretion. In conclusion, the CEK1-mediated MAPK pathway is involved in β-glucan exposure in a fungal pathogen, hence influencing dectin-1-dependent immune cell recognition, thus establishing this fungal intracellular signaling route as a promising novel therapeutic target.
机译：对白色念珠菌的固有免疫力取决于真菌细胞壁上分子模式的识别。但是，主要成分（例如β-葡聚糖）的掩盖似乎是真菌进化出的一种机制，可避免通过dectin-1受体识别免疫细胞。虽然 C的作用。先前已经在动物模型中建立了白色念珠菌丝裂原激活蛋白激酶（MAPK）路径作为毒力决定因素，但这种行为的机制尚不清楚。在这项研究中，我们证明了 C的破坏。白色念珠菌胞外信号调节激酶（ERK）样1（ CEK1 ）介导的MAPK途径导致细胞壁β-葡聚糖暴露增强，与野生型相比，更有效地触发免疫反应，因为通过dectin-1介导的特异性结合以及人类树突状细胞（hDC）和巨噬细胞介导的吞噬作用，细胞内信号传导途径的杀伤和激活进行检测。在分子水平上， CEK1 的破坏导致脾酪氨酸激酶（Syk），Raf-1和ERK1 / 2的活化以及hDC上IκB的降解和dectin-1依赖性激活蛋白的增加1（AP-1）在转染细胞上的激活。另外，与这些改变的途径一致，我们检测到增加了活性氧的产生和细胞因子的分泌。总之， CEK1 介导的MAPK途径参与了真菌病原体中β-葡聚糖的暴露，从而影响了dectin-1依赖性免疫细胞的识别，从而确立了这种真菌细胞内信号转导途径是有前途的新方法治疗目标。

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