Section of Infectious Diseases, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520‐8031, USA.
J Infect Dis. 2010 Dec 15;202(12):1804-12. doi: 10.1086/657416. Epub 2010 Nov 4.
Polymorphonuclear leukocytes (PMNs) are key in innate immunity, but their role in viral pathogenesis is incompletely understood. In infection due to West Nile virus (WNV), we found that expression of 2 PMN-attracting chemokines, Cxcl1 and Cxcl2, was rapidly and dramatically elevated in macrophages. PMNs are rapidly recruited to the site of WNV infection in mice and support efficient replication of WNV. Mice depleted of PMNs after WNV inoculation developed higher viremia and experienced earlier death, compared with the control group, which suggest a protective role for PMNs. In contrast, when PMNs were depleted prior to infection with WNV, and in mice deficient in Cxcr2 (a chemokine receptor gene), viremia was reduced and survival was enhanced. Collectively, these data suggest that PMNs have a biphasic response to WNV infection, serving as a reservoir for replication and dissemination in early infection and later contributing to viral clearance.
多形核白细胞 (PMN) 在先天免疫中起着关键作用,但它们在病毒发病机制中的作用尚不完全清楚。在西尼罗河病毒 (WNV) 感染中,我们发现 PMN 吸引趋化因子 Cxcl1 和 Cxcl2 的表达在巨噬细胞中迅速而显著上调。PMN 被迅速募集到 WNV 感染部位,并支持 WNV 的有效复制。与对照组相比,WNV 接种后 PMN 耗竭的小鼠会出现更高的病毒血症并更早死亡,这表明 PMN 具有保护作用。相比之下,当在感染 WNV 之前耗尽 PMN,并且在 Cxcr2 缺陷(趋化因子受体基因)的小鼠中,病毒血症减少,存活率提高。总的来说,这些数据表明 PMN 对 WNV 感染有双相反应,在早期感染中充当复制和传播的储库,随后有助于清除病毒。