Host insulin stimulates Echinococcus multilocularis insulin signalling pathways and larval development.
Host insulin stimulates Echinococcus multilocularis insulin signalling pathways and larval development.
复制标题
DOI：
10.1186/1741-7007-12-5
复制
发表时间：
2014-01-27
期刊：
影响因子：
5.4
通讯作者：
Brehm K
中科院分区：
文献类型：
--
作者：
Hemer S;Konrad C;Spiliotis M;Koziol U;Schaack D;Förster S;Gelmedin V;Stadelmann B;Dandekar T;Hemphill A;Brehm K
多房棘球绦虫的后绦虫是泡状棘球蚴病的病原体，泡状棘球蚴病是一种致命的人畜共患病。感染是通过在中间宿主的肝脏内建立寄生虫幼虫而开始的，其中存在高浓度的胰岛素，随后是宿主器官中后绦虫的肿瘤样生长。对决定E.多房性或宿主激素对寄生虫增殖的影响知之甚少。使用体外培养系统的寄生虫幼虫，我们表明，生理浓度（10 nM）的人胰岛素显着刺激形成的后绦虫幼虫从寄生虫干细胞和促进无性生长的后绦虫。此外，人胰岛素寄生虫幼虫导致葡萄糖摄取增加和棘球蚴胰岛素信号传导成分，包括胰岛素受体样激酶，EmIR 1，我们证明主要在寄生虫的糖原储存细胞的表达增强的磷酸化。我们还表征了第二个胰岛素受体家族成员EmIR 2，并证明了其配体结合结构域与人胰岛素在酵母双杂交系统中的相互作用。添加胰岛素受体抑制剂导致后绦虫死亡，阻止寄生虫干细胞的后绦虫发育，并通过宿主胰岛素损害胰岛素信号通路的激活。我们的数据表明宿主胰岛素作为宿主肝脏内寄生虫发育的刺激物，并且E。多房菌通过进化上保守的胰岛素信号传导途径感受宿主激素。激素宿主-寄生虫的交叉交流，促进了相对密切的系统发育关系之间E。因此，多房棘球蚴及其哺乳动物宿主在泡状棘球蚴病的病理学中似乎是重要的。这有助于更深入地了解绦虫幼虫感染的器官嗜性和寄生虫持久性。此外，我们的数据表明，棘球绦虫胰岛素信号通路是有前途的目标，为开发新的药物。
The metacestode of the tapeworm Echinococcus multilocularis is the causative agent of alveolar echinococcosis, a lethal zoonosis. Infections are initiated through establishment of parasite larvae within the intermediate host’s liver, where high concentrations of insulin are present, followed by tumour-like growth of the metacestode in host organs. The molecular mechanisms determining the organ tropism of E. multilocularis or the influences of host hormones on parasite proliferation are poorly understood. Using in vitro cultivation systems for parasite larvae we show that physiological concentrations (10 nM) of human insulin significantly stimulate the formation of metacestode larvae from parasite stem cells and promote asexual growth of the metacestode. Addition of human insulin to parasite larvae led to increased glucose uptake and enhanced phosphorylation of Echinococcus insulin signalling components, including an insulin receptor-like kinase, EmIR1, for which we demonstrate predominant expression in the parasite’s glycogen storage cells. We also characterized a second insulin receptor family member, EmIR2, and demonstrated interaction of its ligand binding domain with human insulin in the yeast two-hybrid system. Addition of an insulin receptor inhibitor resulted in metacestode killing, prevented metacestode development from parasite stem cells, and impaired the activation of insulin signalling pathways through host insulin. Our data indicate that host insulin acts as a stimulant for parasite development within the host liver and that E. multilocularis senses the host hormone through an evolutionarily conserved insulin signalling pathway. Hormonal host-parasite cross-communication, facilitated by the relatively close phylogenetic relationship between E. multilocularis and its mammalian hosts, thus appears to be important in the pathology of alveolar echinococcosis. This contributes to a closer understanding of organ tropism and parasite persistence in larval cestode infections. Furthermore, our data show that Echinococcus insulin signalling pathways are promising targets for the development of novel drugs.
登录
查看更多内容
影响因子：
1.3
作者：
Basso, W;Venturini, L;Dubey, JP
通讯作者：
Dubey, JP
影响因子：
4.8
作者：
Hwang, JB;Frost, SC
通讯作者：
Frost, SC
影响因子：
--
作者：
MISBIN, RI;MERIMEE, TJ;LOWENSTEIN, JM
通讯作者：
LOWENSTEIN, JM
影响因子：
5.3
作者：
Assmann, Anke;Ueki, Kohjiro;Kulkarni, Rohit N.
通讯作者：
Kulkarni, Rohit N.
影响因子：
5.8
作者：
Gelmedin, Verena;Caballero-Gamiz, Rocio;Brehm, Klaus
通讯作者：
Brehm, Klaus