Xian Siqi, Chen Lujuan, Yan Yan, Chen Jianfang, Yu Guixia, Shao Yuxiao, Zhan Bin, Wang Yanhai, Zhao Limei
Department of Pathogenic Biology, School of Basic Medical Sciences and Forensic Medicine, Baotou Medical College, Baotou 014040, China.
Department of Pediatrics, National School of Tropical Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Trop Med Infect Dis. 2023 Jan 7;8(1):47. doi: 10.3390/tropicalmed8010047.
As a zoonotic disease caused by larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process 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 calreticulin (CRT), a highly conserved Ca-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 CRTs bound to human C1q, and the interaction of recombinant CRT (rCRT) inhibited C1q binding to IgM. Consequently, rCRT inhibited classical complement activation manifested as decreasing C4/C3 depositions and antibody-sensitized cell lysis. Moreover, rCRT binding to C1q suppressed C1q binding to human mast cell, HMC-1, resulting in reduced C1q-induced mast cell chemotaxis. According to these results, expresses CRT 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.
作为一种由幼虫引起的人畜共患病，泡型包虫病（AE）是最严重的寄生虫感染形式之一。在漫长的进化过程中，它形成了复杂的策略来逃避宿主的免疫攻击并在宿主体内存活。然而，免疫逃避的潜在机制仍不清楚。在此，我们研究了一种高度保守的钙结合蛋白钙网蛋白（CRT）与人补体C1q的结合活性及其抑制经典补体激活的能力。酶联免疫吸附测定（ELISA）、Far Western印迹法和免疫沉淀结果表明，重组CRT和天然CRT均与人C1q结合，并且重组CRT（rCRT）的相互作用抑制了C1q与IgM的结合。因此，rCRT抑制经典补体激活，表现为C4/C3沉积减少和抗体致敏细胞裂解。此外，rCRT与C1q的结合抑制了C1q与人肥大细胞HMC-1的结合，导致C1q诱导的肥大细胞趋化性降低。根据这些结果，泡型包虫表达CRT以干扰C1q介导的补体激活和C1q依赖的免疫细胞非补体激活，这可能是寄生虫在宿主体内的一种免疫逃避策略。
