Department of Pathology, The University of Hong Kong, Hong Kong, China.
Cell Mol Immunol. 2011 Nov;8(6):462-8. doi: 10.1038/cmi.2011.38. Epub 2011 Sep 26.
Interleukin-17 (IL-17), a member of the IL-17 cytokine family, plays a crucial role in mediating the immune response against extracellular bacteria and fungi in the lung. Although there is increasing evidence that IL-17 is involved in protective immunity against H1 and H3 influenza virus infections, little is known about the role of IL-17 in the highly pathogenic H5N1 influenza virus infection. In this study, we show that H5N1-infected IL-17 knockout (KO) mice exhibit markedly increased weight loss, more pronounced lung immunopathology and significantly reduced survival rates as compared with infected wild-type controls. Moreover, the frequency of B cells in the lung were substantially decreased in IL-17 KO mice after virus infection, which correlated with reduced CXCR5 expression in B cells and decreased CXCL13 production in the lung tissue of IL-17 KO mice. Consistent with this observation, B cells from IL-17 KO mice exhibited a significant reduction in chemokine-mediated migration in culture. Taken together, these findings demonstrate a critical role for IL-17 in mediating the recruitment of B cells to the site of pulmonary influenza virus infection in mice.
白细胞介素-17 (IL-17) 是白细胞介素-17 细胞因子家族的成员,在介导肺部针对细胞外细菌和真菌的免疫反应中发挥着关键作用。尽管越来越多的证据表明 IL-17 参与了对 H1 和 H3 流感病毒感染的保护性免疫,但对于 IL-17 在高致病性 H5N1 流感病毒感染中的作用知之甚少。在这项研究中,我们表明 H5N1 感染的白细胞介素-17 敲除 (KO) 小鼠与感染野生型对照相比,体重明显减轻,肺部免疫病理学更严重,存活率显著降低。此外,病毒感染后,IL-17 KO 小鼠肺部的 B 细胞频率显著降低,这与 B 细胞中 CXCR5 表达降低以及 IL-17 KO 小鼠肺组织中 CXCL13 产生减少有关。与这一观察结果一致的是,IL-17 KO 小鼠的 B 细胞在培养中对趋化因子介导的迁移表现出明显减少。综上所述,这些发现表明白细胞介素-17 在介导 B 细胞向肺部流感病毒感染部位募集方面起着关键作用。