Trichinella spiralis Calreticulin S-Domain Binds to Human Complement C1q to Interfere With C1q-Mediated Immune Functions.
Trichinella spiralis Calreticulin S-Domain Binds to Human Complement C1q to Interfere With C1q-Mediated Immune Functions.
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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。
DOI：
10.3389/fimmu.2020.572326
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发表时间：
2020
影响因子：
7.3
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Shao S;Hao C;Zhan B;Zhuang Q;Zhao L;Chen Y;Huang J;Zhu X
蠕虫发展出逃避宿主免疫反应的策略，这有助于它们在敌对的宿主免疫环境中生存。旋毛虫，一种生活在组织中的线虫，已经发展出一种复杂的策略来逃避补体的攻击。我们之前的研究表明，螺旋体分泌钙网蛋白（TsCRT）通过与C1q结合抑制宿主经典补体激活；然而，TsCRT中的C1q结合位点和补体相关免疫逃避的具体机制尚不清楚。通过分子对接建模和片段表达，我们确定TsCRT的153-aa结构域tsct - s负责C1q的结合。在大肠杆菌中表达的重组TsCRT- s蛋白与全长TsCRT具有相同的结合和抑制人c1q诱导的补体和中性粒细胞活化的能力。TsCRT-S通过与C1q结合抑制中性粒细胞活性氧和弹性蛋白酶的释放，降低了新生螺旋体幼虫的中性粒细胞杀伤。TsCRT-S与C1q的结合也抑制了中性粒细胞胞外陷阱（NETs）的形成，NETs与自身免疫性病理有关，尚未成为治疗靶点。这些发现提供了证据，证明TsCRT- s片段，而不是全长TsCRT，是旋毛虫病疫苗或治疗开发以及补体相关自身免疫性疾病治疗的潜在靶标。
Helminths develop strategies to escape host immune responses that facilitate their survival in the hostile host immune environment. Trichinella spiralis, a tissue-dwelling nematode, has developed a sophisticated strategy to escape complement attack. Our previous study demonstrated that T. spiralis secretes calreticulin (TsCRT) to inhibit host classical complement activation through binding to C1q; however, the C1q binding site in TsCRT and the specific mechanism involved with complement-related immune evasion remains unknown. Using molecular docking modeling and fragment expression, we determined that TsCRT-S, a 153-aa domain of TsCRT, is responsible for C1q binding. Recombinant TsCRT-S protein expressed in Escherichia coli had the same capacity to bind and inhibit human C1q-induced complement and neutrophil activation, as full-length TsCRT. TsCRT-S inhibited neutrophil reactive oxygen species and elastase release by binding to C1q and reduced neutrophil killing of newborn T. spiralis larvae. Binding of TsCRT-S to C1q also inhibited formation of neutrophil extracellular traps (NETs), which are involved in autoimmune pathologies and have yet to be therapeutically targeted. These findings provide evidence that the TsCRT-S fragment, rather than the full-length TsCRT, is a potential target for vaccine or therapeutic development for trichinellosis, as well as for complement-related autoimmune disease therapies.
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影响因子：
4.6
作者：
Lund ME;Greer J;Dixit A;Alvarado R;McCauley-Winter P;To J;Tanaka A;Hutchinson AT;Robinson MW;Simpson AM;O'Brien BA;Dalton JP;Donnelly S
通讯作者：
Donnelly S
影响因子：
6.1
作者：
Almzaiel, Anwar J.;Billington, Richard;Moody, A. John
通讯作者：
Moody, A. John
影响因子：
4.8
作者：
Gaboriaud, C;Juanhuix, J;Arlaud, GJ
通讯作者：
Arlaud, GJ
影响因子：
2.2
作者：
Kasper, G;Brown, A;Pritchard, DI
通讯作者：
Pritchard, DI
旋毛虫感染通过程序性死亡 1 介导的免疫调节减轻胶原诱导的关节炎
影响因子：
7.3
作者：
Cheng Y;Zhu X;Wang X;Zhuang Q;Huyan X;Sun X;Huang J;Zhan B;Zhu X
通讯作者：
Zhu X