Dectin-1-Dependent LC3 Recruitment to Phagosomes Enhances Fungicidal Activity in Macrophages
Dectin-1-Dependent LC3 Recruitment to Phagosomes Enhances Fungicidal Activity in Macrophages
复制标题
DOI：
10.1093/infdis/jiu290
复制
发表时间：
2014-12-01
影响因子：
6.4
通讯作者：
Vyas, Jatin M.
中科院分区：
文献类型：
--
作者：
Tam, Jenny M.;Mansour, Michael K.;Vyas, Jatin M.
自噬被认为在哺乳动物宿主防御真菌病原体中发挥作用，尽管分子细节尚不清楚。本研究表明，原代巨噬细胞缺乏自噬因子LC3，在白色念珠菌刺激下，其杀真菌活性降低，但细胞因子产生增加。LC3招募到真菌吞噬体需要激活真菌模式受体dectin-1。LC3向吞噬体的募集也需要Syk信号，但不依赖于toll样受体的所有活性，也不需要接头蛋白Card9的存在。我们进一步证明，NADPH氧化酶产生活性氧是LC3招募到真菌吞噬体所必需的。这些观察结果直接将LC3与巨噬细胞中针对白色念珠菌的炎症途径联系起来。
Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient in the autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production in response to Candida albicans stimulation. LC3 recruitment to fungal phagosomes requires activation of the fungal pattern receptor dectin-1. LC3 recruitment to the phagosome also requires Syk signaling but is independent of all activity by Toll-like receptors and does not require the presence of the adaptor protein Card9. We further demonstrate that reactive oxygen species generation by NADPH oxidase is required for LC3 recruitment to the fungal phagosome. These observations directly link LC3 to the inflammatory pathway against C. albicans in macrophages.