Protective immune responses against West Nile virus are primed by distinct complement activation pathways
Protective immune responses against West Nile virus are primed by distinct complement activation pathways
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DOI：
10.1084/jem.20052388
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发表时间：
2006-05-15
影响因子：
15.3
通讯作者：
Diamond, Michael S.
中科院分区：
文献类型：
--
作者：
Mehlhop, Erin;Diamond, Michael S.
西尼罗河病毒（WNV）在包括人类在内的几种脊椎动物中引起中枢神经系统的严重感染。先前的研究表明，补体在控制补体（C）3（-/-）和补体受体1/2（-/-）小鼠中的WNV感染中起关键作用。在这里，我们剖析了个体补体激活途径对预防西尼罗河病毒疾病的贡献。C1 q、C4、因子B或因子D的遗传缺陷均导致小鼠死亡率增加，表明所有激活途径共同作用以限制WNV传播。在没有替代途径补体激活的情况下，WNV在早期传播到中枢神经系统，并与CD 8（+）T细胞反应降低有关，但接近正常的抗WNV抗体谱。缺乏经典途径和凝集素途径的动物在B和T细胞对西尼罗河病毒的反应中都有缺陷。最后，有些令人惊讶的是，C1 q是脾脏中的生产性感染所必需的，但不是西尼罗河病毒感染后适应性免疫反应的发展所必需的。我们的研究结果表明，个别途径的补体激活控制西尼罗河病毒感染的启动适应性免疫反应，通过不同的机制。
West Nile virus (WNV) causes a severe infection of the central nervous system in several vertebrate animals including humans. Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3(-/-) and complement receptor 1/2(-/-) mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8(+) T cell responses yet near normal anti-WNV antibody profiles. Animals lacking the classical and lectin pathways had deficits in both B and T cell responses to WNV. Finally, and somewhat surprisingly, C1q was required for productive infection in the spleen but not for development of adaptive immune responses after WNV infection. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.