Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation.
Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation.
复制标题
旋毛虫副肌球蛋白结合人补体 C1q 并抑制经典补体激活
DOI：
10.1371/journal.pntd.0004310
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发表时间：
2015-12
影响因子：
3.8
通讯作者：
Zhu X
中科院分区：
文献类型：
--
作者：
Sun R;Zhao X;Wang Z;Yang J;Zhao L;Zhan B;Zhu X
旋毛虫表达副肌球蛋白（Ts-Pmy）作为防御机制。Ts-Pmy是一种功能性蛋白质，具有与人补体C8和C9结合的活性，因此在逃避宿主免疫系统的攻击中起作用。在本研究中，Ts-Pmy与人补体C1 q的结合活性及其抑制经典补体激活的能力进行了研究。分别用ELISA、Far Western blotting和免疫沉淀法检测重组和天然Ts-Pmy与人C1 q的结合。重组Ts-Pmy（rTs-Pmy）与C1 q的结合抑制C1 q与IgM的结合，从而抑制C3沉积。在rTs-Pmy存在下，由经典补体途径引起的抗体致敏红细胞（EA）的溶解也被抑制。除了抑制经典的补体激活，rTs-Pmy还抑制C1 q与THP-1衍生的巨噬细胞的结合，从而减少C1 q诱导的巨噬细胞迁移。我们的结果表明T.螺旋体副肌球蛋白通过与C8和C9以外的C1 q结合来干扰补体激活，从而在免疫逃避中起重要作用。旋毛虫病是世界范围内最重要的食源性人畜共患病之一。旋毛虫在宿主体内生存的关键是躲避免疫防御系统的攻击。我们的前期研究表明旋毛虫副肌球蛋白（Ts-Pmy）通过与人补体C8和C9结合，在逃避宿主免疫攻击中发挥作用。在这里，我们证明了Ts-Pmy通过与人补体C1 q结合来抑制经典补体激活。结果，经典补体途径介导的溶血在Ts-Pmy的存在下被抑制。此外，Ts-Pmy抑制C1 q与THP-1衍生的巨噬细胞的结合和C1 q诱导的巨噬细胞迁移。这些结果表明，旋毛虫副肌球蛋白是一个潜在的免疫调节剂参与逃避宿主补体攻击的结合C1 q除了C8/C9，因此是一个有效的疫苗靶点，对旋毛虫病。
Trichinella spiralis expresses paramyosin (Ts-Pmy) as a defense mechanism. Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host’s immune system. In the present study, the binding activity of Ts-Pmy to human complement C1q and its ability to inhibit classical complement activation were investigated. The binding of recombinant and natural Ts-Pmy to human C1q were determined by ELISA, Far Western blotting and immunoprecipitation, respectively. Binding of recombinant Ts-Pmy (rTs-Pmy) to C1q inhibited C1q binding to IgM and consequently inhibited C3 deposition. The lysis of antibody-sensitized erythrocytes (EAs) elicited by the classical complement pathway was also inhibited in the presence of rTs-Pmy. In addition to inhibiting classical complement activation, rTs-Pmy also suppressed C1q binding to THP-1-derived macrophages, thereby reducing C1q-induced macrophages migration. Our results suggest that T. spiralis paramyosin plays an important role in immune evasion by interfering with complement activation through binding to C1q in addition to C8 and C9. Trichinellosis is one of the most important food-borne parasitic zoonoses worldwide. The key factor for Trichinella spiralis to survive in its host is evading from the attacks by the immune defense system. Our previous study revealed that paramyosin from Trichinella spiralis (Ts-Pmy) played a role in evading host immune attacks by binding to human complement C8 and C9. Here, we demonstrated that Ts-Pmy inhibited classical complement activation by binding to human complement C1q. As a result, classical complement pathway-mediated hemolysis was inhibited in the presence of Ts-Pmy. Additionally, Ts-Pmy inhibited C1q binding to THP-1-derived macrophages and C1q-induced macrophages migration. These results suggest that Trichinella spiralis paramyosin is a potential immunomodulator involved in the evasion of the host complement attack by binding to C1q in addition to C8/C9, and therefore is a potent vaccine target against trichinellosis.