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C. albicans N-linked mannans potentiate the induction of trained immunity via Dectin-2
The Journal of Infectious Diseases ( IF 6.4 ) Pub Date : 2024-03-06 , DOI: 10.1093/infdis/jiae112
Diletta Rosati 1 , Arnab Pradhan 2 , Julia I P van Heck 1 , Leonie Helder 1 , Martin Jaeger 1 , Neil A R Gow 2 , Leo A B Joosten 1, 3 , David L Williams 4 , Alistair J P Brown 2 , Mariolina Bruno 1 , Mihai G Netea 1, 5
Affiliation  

The interaction between the Candida albicans cell wall and pattern recognition receptors is crucial for the initiation of host immune responses which, ultimately, contribute to the clearance of this pathogenic fungus. In the present study, we investigate the ability of C. albicans mannans to modulate immune response and induce innate immune memory (also termed trained immunity). Using mutants of C. albicans that are defective in, or lack mannosyl residues, we show that alterations in the mannosylation of the C. albicans cell wall affect the innate cytokine response and strongly reduce the secretion of T cell-derived cytokines. Subsequently, we demonstrate that the branching of N-linked mannan, but not O-linked mannan, is essential to potentiate the induction of trained immunity, a process mediated by Dectin-2. In conclusion, N-linked mannan is needed, in addition to β-glucans, for an effective induction of trained immunity by C. albicans.

中文翻译:

白色念珠菌 N-连接甘露聚糖通过 Dectin-2 增强训练免疫力的诱导

白色念珠菌细胞壁和模式识别受体之间的相互作用对于宿主免疫反应的启动至关重要,最终有助于清除这种病原真菌。在本研究中,我们研究了白色念珠菌甘露聚糖调节免疫反应和诱导先天免疫记忆(也称为训练免疫)的能力。使用有缺陷或缺乏甘露糖基残基的白色念珠菌突变体,我们发现白色念珠菌细胞壁甘露糖基化的改变会影响先天细胞因子反应并强烈减少 T 细胞衍生的细胞因子的分泌。随后,我们证明 N-连接甘露聚糖的分支,而不是 O-连接甘露聚糖,对于增强训练免疫的诱导至关重要,这是由 Dectin-2 介导的过程。总之,除了 β-葡聚糖之外,还需要 N-连接甘露聚糖来有效诱导白色念珠菌训练有素的免疫力。
更新日期:2024-03-06
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