Echinococcus multilocularis Calreticulin Interferes with C1q-Mediated Complement Activation.
Echinococcus multilocularis Calreticulin Interferes with C1q-Mediated Complement Activation.
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多房棘球绦虫钙网蛋白干扰 C1q 介导的补体激活
DOI：
10.3390/tropicalmed8010047
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发表时间：
2023-01-07
影响因子：
2.9
通讯作者：
中科院分区：
文献类型：
--
作者：
泡状棘球蚴病是由泡状棘球蚴幼虫引起的人畜共患疾病，是寄生虫感染的最严重形式之一。经过漫长的进化过程E. multicularis已经发展出复杂的策略来逃避宿主的免疫攻击并在宿主体内生存。然而，免疫逃避的机制仍不清楚。本文研究了E.多房钙网蛋白（EmCRT），一种高度保守的Ca 2+结合蛋白，与人补体C1 q的结合及其抑制经典补体激活的能力。ELISA、Far Western blotting和免疫沉淀结果表明，重组EmCRT和天然EmCRT均可与人C1 q结合，重组EmCRT（rEmCRT）可抑制C1 q与IgM的结合。因此，rEmCRT抑制经典的补体激活，表现为减少C4/C3沉积和抗体致敏的细胞溶解。此外，rEmCRT与C1 q的结合抑制了C1 q与人肥大细胞HMC-1的结合，导致C1 q诱导的肥大细胞趋化性降低。根据这些结果，E. multicularis表达EmCRT干扰C1 q介导的补体激活和C1 q依赖的非补体激活的免疫细胞，可能作为寄生虫在宿主中的免疫逃避策略。
As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca2+-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, and the interaction of recombinant EmCRT (rEmCRT) inhibited C1q binding to IgM. Consequently, rEmCRT inhibited classical complement activation manifested as decreasing C4/C3 depositions and antibody-sensitized cell lysis. Moreover, rEmCRT binding to C1q suppressed C1q binding to human mast cell, HMC-1, resulting in reduced C1q-induced mast cell chemotaxis. According to these results, E. multilocularis expresses EmCRT to interfere with C1q-mediated complement activation and C1q-dependent non-complement activation of immune cells, possibly as an immune evasion strategy of the parasite in the host.
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影响因子：
2.2
作者：
Kasper, G;Brown, A;Pritchard, DI
通讯作者：
Pritchard, DI
影响因子：
20.3
作者：
Edelson, BT;Stricker, TP;Zutter, MM
通讯作者：
Zutter, MM
旋毛虫钙网蛋白 S 结构域与人补体 C1q 结合，干扰 C1q 介导的免疫功能。
影响因子：
7.3
作者：
Shao S;Hao C;Zhan B;Zhuang Q;Zhao L;Chen Y;Huang J;Zhu X
通讯作者：
Zhu X
影响因子：
2.9
作者：
Gadjeva, Mihaela G.;Rouseva, Marieta M.;Kojouharova, Mihaela S.
通讯作者：
Kojouharova, Mihaela S.
影响因子：
6.7
作者：
Garcia BL;Zhi H;Wager B;Höök M;Skare JT
通讯作者：
Skare JT