A teleost CD46 is involved in the regulation of complement activation and pathogen infection.
A teleost CD46 is involved in the regulation of complement activation and pathogen infection.
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硬骨鱼 CD46 参与补体激活和病原体感染的调节
DOI：
10.1038/s41598-017-15124-y
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发表时间：
2017-11-03
影响因子：
4.6
通讯作者：
Sun L
中科院分区：
文献类型：
--
作者：
Li MF;Sui ZH;Sun L
在哺乳动物中，CD46 参与因子 I (FI) 导致的补体失活。在硬骨鱼中，对CD46功能的研究非常有限。在这项研究中，我们检查了舌鳎（一种具有重要经济价值的硬骨鱼物种）的 CD46 分子 (CsCD46) 的免疫学特性。我们发现重组 CsCD46 (rCsCD46) 与 FI 相互作用并以 FI 依赖性方式抑制补体激活。 rCsCD46 还通过与 FI 相互作用不同的机制与细菌病原体相互作用，涉及不同的 rCsCD46 位点。细胞研究表明，CsCD46 在外周血白细胞 (PBL) 上表达，并保护细胞免受补体的杀伤作用。当细胞与细菌病原体孵育之前用抗体阻断 PBL 上的 CsCD46 时，细胞感染显着减少。一致地，当舌鳎在 rCsCD46 存在的情况下被细菌病原体感染时，病原体的组织传播和存活被显着抑制。这些结果提供了第一个证据，表明硬骨鱼中的 CD46 通过 FI 负向调节补体激活，并保护宿主细胞免受补体诱导的损伤，并且 CD46 可能是通过充当细菌受体来实现最佳细菌感染所必需的。
In mammals, CD46 is involved in the inactivation of complement by factor I (FI). In teleost, study on the function of CD46 is very limited. In this study, we examined the immunological property of a CD46 molecule (CsCD46) from tongue sole, a teleost species with important economic value. We found that recombinant CsCD46 (rCsCD46) interacted with FI and inhibited complement activation in an FI-dependent manner. rCsCD46 also interacted with bacterial pathogens via a different mechanism to that responsible for the FI interaction, involving different rCsCD46 sites. Cellular study showed that CsCD46 was expressed on peripheral blood leukocytes (PBL) and protected the cells against the killing effect of complement. When the CsCD46 on PBL was blocked by antibody before incubation of the cells with bacterial pathogens, cellular infection was significantly reduced. Consistently, when tongue sole were infected with bacterial pathogens in the presence of rCsCD46, tissue dissemination and survival of the pathogens were significantly inhibited. These results provide the first evidence to indicate that CD46 in teleosts negatively regulates complement activation via FI and protects host cells from complement-induced damage, and that CD46 is required for optimal bacterial infection probably by serving as a receptor for the bacteria.
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