State Key Laboratory of Virology, Department of Immunology and Hubei Province, Key Laboratory of Allergy and Immune-Related Diseases, Wuhan University School of Medicine, Wuhan, PR China.
J Innate Immun. 2012;4(3):312-24. doi: 10.1159/000335670. Epub 2012 Mar 2.
L-ficolin, one of the complement lectins found in human serum, is a novel pattern recognition molecule that can specifically bind to microbial carbohydrates, thereby activating the lectin complement pathway and mounting a protective innate immune response. However, little is known about the role of L-ficolin during viral infections in vivo. In the present study, we used a mouse model of influenza A virus infection to demonstrate that the administration of exogenous L-ficolin or ficolin A (FCNA - an L-ficolin-like molecule in the mouse) is protective against the virus. Furthermore, FCNA-null mice have a greatly increased susceptibility to infection with the influenza A virus. Moreover, we found recombinant human L-ficolin inhibited influenza A virus entry into Madin-Darby canine kidney cells. More importantly, L-ficolin can recognize and bind hemagglutinin (HA) and neuraminidase (NA) glycoproteins and different subtypes of influenza A virus, and these interactions can be competitively inhibited by N-acetyl-D-glucosamine. In addition, the binding of L-ficolin and FCNA may lead to the activation of the lectin complement pathway. To our knowledge, this is the first report demonstrating that L-ficolin can block influenza virus infections both in vitro and in vivo using FCNA-knockout mice, possibly by interacting with the carbohydrates of HA and NA. Therefore, these data may provide new immunotherapeutic strategies based on the innate immune molecule L-ficolin against the influenza A virus.
人血清中的补体凝集素 L- ficolin 是一种新型的模式识别分子，能够特异性结合微生物碳水化合物，从而激活凝集素补体途径并引发保护性的固有免疫反应。然而，关于 L- ficolin 在体内病毒感染过程中的作用知之甚少。在本研究中，我们使用流感 A 病毒感染的小鼠模型证明，外源性 L- ficolin 或 ficolin A（FCNA- 小鼠中的一种 L- ficolin 类似物）的给药可抵抗该病毒。此外，FCNA 基因敲除小鼠对流感 A 病毒感染的易感性大大增加。此外，我们发现重组人 L- ficolin 可抑制流感 A 病毒进入 Madin-Darby 犬肾细胞。更重要的是，L- ficolin 可以识别和结合血凝素 (HA) 和神经氨酸酶 (NA) 糖蛋白以及不同亚型的流感 A 病毒，并且这些相互作用可以被 N-乙酰-D-葡萄糖胺竞争性抑制。此外，L- ficolin 和 FCNA 的结合可能导致凝集素补体途径的激活。据我们所知，这是第一项使用 FCNA 基因敲除小鼠证明 L- ficolin 可以在体外和体内阻断流感病毒感染的报告，这可能是通过与 HA 和 NA 的碳水化合物相互作用实现的。因此，这些数据可能为基于固有免疫分子 L- ficolin 针对流感 A 病毒提供新的免疫治疗策略。
