Mehlhop Erin, Diamond Michael S
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Exp Med. 2006 May 15;203(5):1371-81. doi: 10.1084/jem.20052388. Epub 2006 May 1.
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.
西尼罗河病毒（WNV）可在包括人类在内的多种脊椎动物中引发严重的中枢神经系统感染。先前的研究表明，补体在补体（C）3基因敲除小鼠和补体受体1/2基因敲除小鼠中对控制WNV感染起着关键作用。在此，我们剖析了各个补体激活途径对预防WNV疾病的作用。C1q、C4、B因子或D因子的基因缺陷均导致小鼠死亡率增加，这表明所有激活途径共同发挥作用以限制WNV的传播。在缺乏替代途径补体激活的情况下，WNV在更早的时间扩散到中枢神经系统，并且与CD8 + T细胞反应减少但抗WNV抗体谱接近正常有关。缺乏经典途径和凝集素途径的动物对WNV的B细胞和T细胞反应均存在缺陷。最后，有点令人惊讶的是，C1q是脾脏中产生有效感染所必需的，但不是WNV感染后适应性免疫反应发展所必需的。我们的结果表明，补体激活的各个途径通过不同机制启动适应性免疫反应来控制WNV感染。
