Macrophage-Expressed Perforins Mpeg1 and Mpeg1.2 Have an Anti-Bacterial Function in Zebrafish
Macrophage-Expressed Perforins Mpeg1 and Mpeg1.2 Have an Anti-Bacterial Function in Zebrafish
复制标题
巨噬细胞表达的穿孔素Mpeg1和Mpeg1.2在斑马鱼中具有抗菌功能
DOI：
10.1159/000366103
复制
发表时间：
2015-01-01
影响因子：
5.3
通讯作者：
Meijer, Annemarie H.
中科院分区：
文献类型：
--
作者：
Benard, Erica L.;Racz, Peter I.;Meijer, Annemarie H.
巨噬细胞表达基因1（MPEG 1）编码一个进化上保守的蛋白质，具有预测的膜攻击复合物/穿孔素结构域，与宿主防御入侵病原体有关。在脊椎动物中，MPEG 1/穿孔素-2是巨噬细胞的一种膜蛋白，被怀疑参与通过成孔活性杀死细胞内细菌。斑马鱼有3个拷贝的MPEG 1; 2在巨噬细胞中表达，而第三个可能是假基因。mpeg 1和mpeg1.2基因在斑马鱼胚胎感染细菌病原体海洋分枝杆菌和鼠伤寒沙门氏菌期间显示差异调节。虽然mpeg 1在感染两种病原体时下调，但mpeg1.2是感染诱导型的。mpeg1.2的上调部分依赖于功能性Mpeg 1的存在，并且需要Toll样受体衔接分子MyD 88和转录因子NF κ B。mpegl的敲低改变了对M.海水感染，导致细菌负荷增加。在鼠伤寒沙门氏菌感染中，mpeg 1和mpeg1.2敲低均增加细菌负荷，但mpeg 1变形子显示存活时间增加。这两种体内感染模型的综合结果支持MPEG 1/穿孔素-2家族的抗菌功能，并表明两种mpeg 1拷贝的复杂交叉调节有助于斑马鱼宿主对抗各种病原体的感染。(C)2014 S. Karger AG，巴塞尔
Macrophage-expressed gene 1 (MPEG1) encodes an evolutionarily conserved protein with a predicted membrane attack complex/perforin domain associated with host defence against invading pathogens. In vertebrates, MPEG1/perforin-2 is an integral membrane protein of macrophages, suspected to be involved in the killing of intracellular bacteria by pore-forming activity. Zebrafish have 3 copies of MPEG1; 2 are expressed in macrophages, whereas the third could be a pseudogene. The mpeg1 and mpeg1.2 genes show differential regulation during infection of zebrafish embryos with the bacterial pathogens Mycobacterium marinum and Salmonella typhimurium. While mpeg1 is downregulated during infection with both pathogens, mpeg1.2 is infection inducible. Upregulation of mpeg1.2 is partially dependent on the presence of functional Mpeg1 and requires the Toll-like receptor adaptor molecule MyD88 and the transcription factor NF kappa B. Knockdown of mpegl alters the immune response to M. marinum infection and results in an increased bacterial burden. In Salmonella typhimurium infection, both mpeg1 and mpeg1.2 knockdown increase the bacterial burdens, but mpeg1 morphants show increased survival times. The combined results of these two in vivo infection models support the anti-bacterial function of the MPEG1/perforin-2 family and indicate that the intricate cross-regulation of the two mpeg1 copies aids the zebrafish host in combatting infection of various pathogens. (C) 2014 S. Karger AG, Basel