Role of eosinophils and apoptosis in PDIMs/PGLs deficient mycobacterium elimination in adult zebrafish
Role of eosinophils and apoptosis in PDIMs/PGLs deficient mycobacterium elimination in adult zebrafish
复制标题
嗜酸性粒细胞和细胞凋亡在成年斑马鱼分枝杆菌消除缺陷的 PDIM/PGL 中的作用
DOI：
10.1016/j.dci.2016.02.007
复制
发表时间：
2016-06-01
影响因子：
2.9
通讯作者：
Wang, Decheng
中科院分区：
文献类型：
--
作者：
Huang, Xinhua;Wang, Hui;Wang, Decheng
细胞壁脂质Phthiocerol dimycerosates（PDIM）及其结构相关化合物酚糖脂（PGLs）是分枝杆菌的主要毒力因子，如在各种动物模型中PDIM/PGLs缺陷突变体的生长减少所示。PDIM/PGLs在调节宿主免疫应答中起着积极的作用。然而，PDIM/PGLs缺陷突变体在体内如何被消除的细胞和分子机制仍然是难以捉摸的。我们的目的是研究什么样的宿主免疫应答对体内分枝杆菌的清除有影响。利用基因芯片，我们发现PDIMs/PGLs调节不同的宿主反应，包括趋化和粘着斑的下游途径和凋亡。我们通过Diff-Quik染色，结合透射电镜和TUNEL染色分别检测这两种宿主反应。超微结构观察显示，嗜酸性粒细胞在WT感染的斑马鱼中于第1天出现，而在PDIM/PGLs缺陷型MUR感染的动物中，嗜酸性粒细胞的出现延迟至第7天。更有趣的是，在感染后第1天，PDIM/PGLs突变体感染的斑马鱼中细胞凋亡显著增加，与此时WT感染的鱼相比。然而，细胞凋亡的趋势完全逆转，与PDIM/PGLs缺陷突变体相比，WT感染的斑马鱼中检测到更多的细胞凋亡，尤其是肉芽肿内的更多细胞凋亡。本研究表明PDIM/PGLs的抗凋亡作用和在斑马鱼感染早期组织中嗜酸性粒细胞的募集可能促进细菌在体内的生长。(C)2016爱思唯尔有限公司版权所有
The cell wall lipids phthiocerol dimycocerosates (PDIMs) and its structurally-related compound, phenolic glycolipids (PGLs) are major virulence factors of mycobacterium, as shown by the reduced growth of PDIMs/PGLs deficient mutants in various animal models. PDIMs/PGLs play active roles in modulating host immune responses. However, the cellular and molecular mechanisms of how PDIMs/PGLs deficient mutant was eliminated in vivo are still elusive. Our aim was to investigate what host immune responses have effect on mycobacterium elimination in vivo. Using microarray, we find PDIMs/PGLs modulate divergent host responses, including chemotaxis and focal adhesion's downstream pathway and apoptosis. We examine these two host responses by Diff-Quik stain, coupled with transmission electron microscopy and TUNEL stain respectively. The ultrastructure observation showed that eosinophils appeared in WT-infected zebrafish at day 1, however eosinophils arrived was delayed to day 7 in PDIMs/PGLs-deficient mutant-infected animals. More intriguingly, apoptosis was markedly increased in PDIMs/PGLs-mutant infected zebrafish at day 1 after infection, compared to WT-infected fishes at this time. However, apoptosis trend was fully reversed by day 7, with increased apoptosis were detected in WT-infected zebrafish compared with the PDIMs/PGLs-deficient mutant, especially more apoptosis within the granuloma. This study shows that the anti-apoptotic effects of PDIMs/PGLs and the recruitment of eosinophils in tissue during the early infection in zebrafish might promote bacterium growth in vivo. (C) 2016 Elsevier Ltd. All rights reserved.