Functional Genomics of Tick Thioester-Containing Proteins Reveal the Ancient Origin of the Complement System
Functional Genomics of Tick Thioester-Containing Proteins Reveal the Ancient Origin of the Complement System
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DOI：
10.1159/000328851
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发表时间：
2011-10-01
影响因子：
5.3
通讯作者：
Kopacek, Petr
中科院分区：
文献类型：
--
作者：
Buresova, Veronika;Hajdusek, Ondrej;Kopacek, Petr
蜱是重要的体外寄生虫，也是多种人类和动物疾病的传播媒介。蜱的强制性吸血为寄生虫从一个宿主传播到另一个宿主提供了一条强大的途径。蜱虫体内的寄生虫生存依赖于病原体逃避或抑制蜱虫免疫防御的能力，但蜱虫与其病原体之间的分子相互作用仍然知之甚少。在这里，我们报告蜱基因组的独特之处在于它们包含所有已知类别的 α(2)-巨球蛋白家族 (α(2)M-F) 蛋白：α(2)-巨球蛋白泛蛋白酶抑制剂、C3 补体成分以及含昆虫硫酯和巨球蛋白相关蛋白。通过在硬蜱蓖麻硬蜱中使用 RNA 干扰介导的基因沉默，我们证明了 C3 样分子在细菌吞噬作用中的核心作用，并揭示了 α(2)M-F 蛋白的非冗余功能。对单个生物体中 α(2)M-F 功能的评估应显着有助于了解补体系统的进化和功能的一般知识。重要的是，了解蜱免疫机制应该为有效阻断蜱传疾病的传播提供新概念。版权所有 (C) 2011 S. Karger AG，巴塞尔
Ticks are important ectoparasites and vectors of multiple human and animal diseases. The obligatory hemophagy of ticks provides a formidable route for parasite transmission from one host to another. Parasite survival inside the tick relies on the ability of a pathogen to escape or inhibit tick immune defenses, but the molecular interactions between the tick and its pathogens remain poorly understood. Here we report that tick genomes are unique in that they contain all known classes of the alpha(2)-macroglobulin family (alpha(2)M-F) proteins: alpha(2)-macroglobulin pan-protease inhibitors, C3 complement components, and insect thioester-containing and macroglobulin-related proteins. By using RNA interference-mediated gene silencing in the hard tick Ixodes ricinus we demonstrated the central role of a C3-like molecule in the phagocytosis of bacteria and revealed nonredundant functions for alpha(2)M-F proteins. Assessment of alpha(2)M-F functions in a single organism should significantly contribute to the general knowledge on the evolution and function of the complement system. Importantly, understanding the tick immune mechanisms should provide new concepts for efficient transmission blocking of tick-borne diseases. Copyright (C) 2011 S. Karger AG, Basel