Dendritic cell-associated C-type lectin 1 (Dectin-1, also known as CLEC7A) is an innate immune pattern recognition receptor that recognizes β-glucan on the Candida albicans cell wall. Recognition of β-glucan by immune cells leads to phagocytosis, oxidative burst, cytokine and chemokine production. We looked for specific mechanisms that coordinate phagocytosis downstream of Dectin-1 leading to actin reorganization and internalization of fungus. We found that stimulation of Dectin-1 by soluble β-glucan leads to mechanical force generation and areal contraction in Dectin-1-transfected HEK-293 cells and M1 macrophages. With inhibitor studies, we found this force generation is a spleen tyrosine kinase (SYK)-independent, but SRC family kinase (SFK)-dependent process mediated through the RHOA-ROCK-myosin light chain (MLC) pathway. We confirmed activation of RHOA downstream of Dectin-1 using activity assays and stress fiber formation. Through phagocytosis assays, we found direct evidence for the importance of RHOA-ROCK-MLC signaling in the process of phagocytosis of C. albicans.

中文翻译：

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通过 Dectin-1 产生 RHOA 介导的机械力。

树突状细胞相关的 C 型凝集素 1（Dectin-1，也称为 CLEC7A）是一种先天免疫模式识别受体，可识别白色念珠菌细胞壁上的 β-葡聚糖。免疫细胞对 β-葡聚糖的识别导致吞噬作用、氧化爆发、细胞因子和趋化因子的产生。我们寻找协调 Dectin-1 下游吞噬作用的特定机制，从而导致肌动蛋白重组和真菌内化。我们发现，可溶性 β-葡聚糖刺激 Dectin-1 会导致 Dectin-1 转染的 HEK-293 细胞和 M1 巨噬细胞产生机械力和面积收缩。通过抑制剂研究，我们发现这种力的产生是不依赖于脾酪氨酸激酶（SYK），但依赖于 SRC 家族激酶（SFK）的过程，通过 RHOA-ROCK-肌球蛋白轻链（MLC）途径介导。我们通过活性测定和应力纤维形成证实了 Dectin-1 下游 RHOA 的激活。通过吞噬实验，我们发现了 RHOA-ROCK-MLC 信号在白色念珠菌吞噬过程中重要性的直接证据。