Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity
Natural antibody and complement mediate neutralization of influenza virus in the absence of prior immunity
复制标题
DOI：
10.1128/jvi.02128-06
复制
发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Carroll, Michael C.
中科院分区：
文献类型：
--
作者：
Jayasekera, Jerome P.;Moseman, E. Ashley;Carroll, Michael C.
早期控制病毒复制的先天免疫反应是必不可少的，以允许时间产生更有效的适应性免疫反应。作为先天免疫的重要组成部分，补体已被证明是防止许多微生物感染所必需的。本研究旨在探讨补体在中和流感病毒中的作用。结果证实了补体介导的流感病毒血清中和的经典途径。虽然非免疫血清中和流感病毒，但病毒中和（VN）机制需要抗体，因为rag1缺陷小鼠血清缺乏VN活性；此外，纯化的天然免疫球蛋白M （IgM）可以恢复抗体缺乏血清的VN活性。天然IgM和补体对VN的作用机制与病毒粒子聚集和病毒血凝素受体的包被有关；然而，病毒裂解对VN无显著影响。此外，rag1缺陷小鼠重组天然IgM导致流感病毒感染期间延迟发病。总的来说，这些结果提供了证据，证明天然IgM和补体经典途径的早期成分协同作用，以中和流感病毒，这种相互作用可能对流感病毒性肺炎的病程产生重大影响。
Early control of virus replication by the innate immune response is essential to allow time for the generation of a more effective adaptive immune response. As an important component of innate immunity, complement has been shown to be necessary for protection against numerous microbial infections. This study was undertaken to investigate the role of complement in neutralizing influenza virus. Results demonstrated that the classical pathway of complement mediated serum neutralization of influenza virus. Although nonimmune serum neutralized influenza virus, the mechanism of virus neutralization (VN) required antibody, as sera from RAG1-deficient mice lacked VN activity; moreover, purified natural immunoglobulin M (IgM) restored VN activity to antibody-deficient sera. The mechanism of VN by natural IgM and complement was associated with virion aggregation and coating of the viral hemagglutinin receptor; however, viral lysis did not significantly contribute to VN. Additionally, reconstitution of RAG1-deficient mice with natural IgM resulted in delayed morbidity during influenza virus infection. Collectively, these results provide evidence that natural IgM and the early components of the classical pathway of complement work in concert to neutralize influenza virus and that this interaction may have a significant impact on the course of influenza viral pneumonia.