Schistosoma japonicum egg specific protein SjE16.7 recruits neutrophils and induces inflammatory hepatic granuloma initiation.
Schistosoma japonicum egg specific protein SjE16.7 recruits neutrophils and induces inflammatory hepatic granuloma initiation.
复制标题
日本血吸虫卵特异性蛋白 SjE16.7 招募中性粒细胞并诱导炎症性肝肉芽肿发生
DOI：
10.1371/journal.pntd.0002703
复制
发表时间：
2014-02
影响因子：
3.8
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Wu C;Chen Q;Fang Y;Wu J;Han Y;Wang Y;Yang Y;Chu M;Feng Y;Tan L;Guo X;Hu W;Wang Z
中性粒细胞在日本血吸虫虫卵肉芽肿性病变中起主要作用，但虫卵募集或激活中性粒细胞的确切机制尚不清楚。在这里，我们报告S。日本血吸虫虫卵特异性EF-手蛋白-SjE16.7是一种有效的中性粒细胞募集剂，并在血吸虫病中引发虫卵相关的炎性肉芽肿。结果表明，SjE16.7在mRNA和蛋白水平的表达仅限于卵期。它位于毛蚴和卵的下壳区，可由卵分泌。SjE16.7的抗原特性强烈表明SjE16.7作为卵源性分子参与宿主-寄生虫相互作用的作用。为了研究SjE16.7在体内的功能，我们用重组SjE16.7攻击小鼠气囊。结果显示，SjE16.7比载体或对照蛋白抑制更多的炎性细胞浸润。使用小鼠腹腔渗出液中性粒细胞，我们发现，SjE16.7显着诱导中性粒细胞在体外的趋化性，所观察到的表型与增强的Rac GT3活化在SjE16.7处理的细胞。最后，体内肝肉芽肿形成模型显示SjE16.7偶联珠粒比对照珠粒募集更多的炎性细胞浸润。提示SjE16.7是一种重要的鸡源性致病因子。通过募集中性粒细胞和诱导局部炎症，SjE16.7促进虫卵通过肠道组织排出，并引发肝脏病理学;因此SjE16.7是预防和治疗血吸虫病的可能靶点。作为一种被忽视的疾病，血吸虫病仍然是全世界寄生虫病和死亡的一个重要原因。日本血吸虫是人类血吸虫病的主要病原体之一。S.日本血吸虫卵是感染后病理的主要原因。它们诱导宿主产生强烈的免疫反应，促进虫卵从组织进入肠腔，导致肝脏病变。本文首次描述了S.日本血吸虫虫卵特异性EF-手蛋白-SjE16.7是一种有效的中性粒细胞募集剂，并在血吸虫病中引发虫卵相关的炎性肉芽肿。这项研究提出了一个精确的机制，鸡蛋招募中性粒细胞和诱导炎症反应。它进一步加深了我们对人类血吸虫病免疫发病机制的理解。此外，它为预防和治疗这种全球重要的寄生虫提供了一个潜在的目标。
Neutrophils are known to play a major role in the egg granulomatous lesions caused by Schistosoma japonicum, but the precise mechanism by which eggs recruit or active neutrophil is unknown. Here we report S. japonicum egg specific EF-hand protein-SjE16.7 is a potent neutrophil recruiter and initiates the egg associated inflammatory granuloma in schistosomiasis. We show that the expression of SjE16.7 at level of both mRNA and protein is restricted to the egg stage. It locates in the miracidium and subshell area of the egg and can be secreted by the egg. The antigenic properties of SjE16.7 strongly suggest a role for SjE16.7 as an egg-derived molecule involved in host-parasite interactions. To study SjE16.7 functions in vivo, we challenged murine air pouch with recombinant SjE16.7. The results showed SjE16.7 trigged more inflammatory cell infiltration than vehicle or control protein. Using peritoneal exudate neutrophils from mice, we found that SjE16.7 significantly induced neutrophil chemotaxis in vitro, and the observed phenotypes were associated with enhanced Rac GTPase activation in SjE16.7 treated cells. Finally, in vivo hepatic granuloma formation model showed SjE16.7 coupled beads recruited more inflammatory cell infiltration than control beads. Our findings suggest SjE16.7 is an important pathogenic factor derived from egg. By recruiting neutrophils and inducing local inflammation, SjE16.7 facilitates eggs to be excreted through gut tissues and also initiates pathology in the liver; therefore SjE16.7 is a possible target for the prevention and treatment of schistosomiasis. As a neglected disease, schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. Schistosoma japonicum is one of the major causative agents of human schistosomiasis. Trapped in the liver or intestinal tissue, S. japonicum eggs are the main cause of pathology following infection. They induce vigorous immune responses from the host, which facilitate the passage of the eggs from the tissue to the gut lumen and cause the pathology in liver. In this paper, we described, for the first time, S. japonicum egg specific EF-hand protein-SjE16.7 is a potent neutrophil recruiter and initiates the egg associated inflammatory granuloma in schistosomiasis. This study presents a precise mechanism by which eggs recruit neutrophil and induce inflammatory response. It furthers our understanding of the immunopathogenesis of human schistosomiasis. In addition, it provides a potential target for the prevention and treatment of this globally important parasite.
登录
查看更多内容
影响因子：
7.3
作者：
Hams E;Aviello G;Fallon PG
通讯作者：
Fallon PG
影响因子：
5.5
作者：
Chuah, Candy;Jones, Malcolm K.;Gobert, Geoffrey N.
通讯作者：
Gobert, Geoffrey N.
影响因子：
1.5
作者：
Schramm, G;Gronow, A;Doenhoff, MJ
通讯作者：
Doenhoff, MJ
影响因子：
2.1
作者：
OWHASHI, M;HORII, Y;ISHII, A
通讯作者：
ISHII, A
影响因子：
4.3
作者：
Van de Vijver, KK;Deelder, AM;Hokke, CH
通讯作者：
Hokke, CH