Key Points OnMBL was able to bind and agglutinate with pathogens. OnMBL was able to significantly reduce the proliferation of pathogens. OnMBL could promote phagocytosis of macrophages with OnCRT interaction. The innate immune system is an ancient defense system in the process of biological evolution, which can quickly and efficiently resist pathogen infection. In mammals, mannose-binding lectin (MBL) is a key molecule in the innate immune and plays an essential role in the first line of host defense against pathogenic bacteria. However, the evolutionary origins and ancient roles of immune defense of MBL and its mechanism in clearance of microbial pathogens are still unclear, especially in early vertebrates. In this study, Oreochromis niloticus MBL (OnMBL) was successfully isolated and purified from the serum of Nile tilapia (O. niloticus). The OnMBL was able to bind and agglutinate with two important pathogens of tilapia, Streptococcus agalactiae and Aeromonas hydrophila. Interestingly, the OnMBL was able to significantly inhibit the proliferation of pathogenic bacteria and reduce the inflammatory response. Upon bacterial challenge, the downregulation of OnMBL expression by RNA interference could lead to rapid proliferation of the pathogenic bacteria, ultimately resulting in tilapia death. However, the phenotype was rescued by reinjection of the OnMBL, which restored the healthy status of the knockdown tilapia. Moreover, a mechanistic analysis revealed that the OnMBL could clear pathogenic bacteria by collaborating with cell-surface calreticulin to facilitate phagocytosis in a complement activation-independent manner. To our knowledge, these results provide the first evidence on the antibacterial response mechanism of MBL performing evolutionary conserved function to promote opsonophagocytosis of macrophages in early vertebrates and reveals new insights into the understanding of the evolutionary origins and ancient roles basis of the C-type lectins in the innate immune defense.

中文翻译：

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甘露糖结合凝集素在早期脊椎动物中具有凝集活性并促进巨噬细胞与钙网蛋白相互作用的调理吞噬作用

关键点 OnMBL 能够与病原体结合并凝集。OnMBL 能够显着减少病原体的增殖。OnMBL 可以通过 OnCRT 相互作用促进巨噬细胞的吞噬作用。先天免疫系统是生物进化过程中一种古老的防御系统，可以快速有效地抵抗病原体感染。在哺乳动物中，甘露糖结合凝集素 (MBL) 是先天免疫中的关键分子，在宿主抵御病原菌的第一道防线中起着至关重要的作用。然而，MBL 免疫防御的进化起源和古老作用及其清除微生物病原体的机制仍不清楚，尤其是在早期脊椎动物中。本研究从尼罗罗非鱼 (O. niloticus) 的血清中成功分离纯化出 Oreochromis niloticus MBL (OnMBL)。OnMBL 能够与罗非鱼的两种重要病原体无乳链球菌和嗜水气单胞菌结合并凝集。有趣的是，OnMBL 能够显着抑制病原菌的增殖并减少炎症反应。在受到细菌攻击时，RNA 干扰对 OnMBL 表达的下调可导致病原菌快速增殖，最终导致罗非鱼死亡。然而，通过重新注射 OnMBL 挽救了表型，这恢复了敲除罗非鱼的健康状态。此外，机制分析表明，OnMBL 可以通过与细胞表面钙网蛋白合作以不依赖补体激活的方式促进吞噬作用来清除病原菌。据我们所知，