Gliotoxin promotes Aspergillus fumigatus internalization into type II human pneumocyte A549 cells by inducing host phospholipase D activation

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• 作者：Xiaodong Jia^a ; ¹ ; Fangyan Chen^a ; ¹ ; Weihua Pan^b ; ¹ ; Rentao Yu^a ; ^c ; Shuguang Tian^a ; Gaige Han^a ; Haiqin Fang^a ; Shuo Wang^a ; Jingya Zhao^a ; Xianping Li^a ; Dongyu Zheng^a ; Sha Tao^a ; Wanqing Liao^b ; Xuelin Han^a ; ^{yilin791228@126.com" class="auth_mail} ; Li Han^a ; ^{hanli@bmi.ac.cn" class="auth_mail} ; ^{hanlicdc@163.com" class="auth_mail}
• 关键词：Gliotoxin ; Aspergillus fumigatus ; Internalization ; Phospholipase D
• 刊名：Microbes and Infection
• 出版年：June 2014
• 年：2014
• 卷：16
• 期：6
• 页码：491-501
• 全文大小：1647 K

文摘

The internalization of Aspergillus fumigatus into lung epithelial cells is critical for the infection process in the host. Gliotoxin is the most potent toxin produced by A. fumigatus. However, its role in A. fumigatus internalization into the lung epithelial cells is still largely unknown. In the present study, the deletion of the gliP gene regulating the production of gliotoxin in A. fumigatus suppressed the internalization of conidia into the A549 lung epithelial cells, and this suppression could be rescued by the exogenous addition of gliotoxin. At lower concentrations, gliotoxin enhanced the internalization of the conidia of A. fumigatus into A549 cells; in contrast, it inhibited the phagocytosis of J774 macrophages in a dose-dependent manner. Under a concentration of 100 ng/ml, gliotoxin had no effect on A549 cell viability but attenuated ROS production in a dose-dependent manner. Gliotoxin significantly stimulated the phospholipase D activity in the A549 cells at a concentration of 50 ng/ml. This stimulation was blocked by the pretreatment of host cells with PLD1- but not PLD2-specific inhibitor. Morphological cell changes induced by gliotoxin were observed in the A549 cells accompanying with obvious actin cytoskeleton rearrangement and a moderate alteration of phospholipase D distribution. Our data indicated that gliotoxin might be responsible for modulating the A. fumigatus internalization into epithelial cells through phospholipase D1 activation and actin cytoskeleton rearrangement.