Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
EMBO Mol Med. 2014 Jan;6(1):120-40. doi: 10.1002/emmm.201302890.
Postinfluenza pneumococcal pneumonia is a common cause of death in humans. However, the role of IL-27 in the pathogenesis of secondary pneumococcal pneumonia after influenza is unknown. We now report that influenza infection induced pulmonary IL-27 production in a type I IFN-α/β receptor (IFNAR) signalling-dependent manner, which sensitized mice to secondary pneumococcal infection downstream of IFNAR pathway. Mice deficient in IL-27 receptor were resistant to secondary pneumococcal infection and generated more IL-17A-producing γδ T cells but not αβ T cells, thereby leading to enhanced neutrophil response during the early phase of host defence. IL-27 treatment could suppress the development of IL-17A-producing γδ T cells activated by Streptococcus pneumoniae and dendritic cells. This suppressive activity of IL-27 on γδ T cells was dependent on transcription factor STAT1. Finally, neutralization of IL-27 or administration of IL-17A restored the role of γδ T cells in combating secondary pneumococcal infection. Our study defines what we believe to be a novel role of IL-27 in impairing host innate immunity against pneumococcal infection.
流感后肺炎球菌性肺炎是人类常见的死亡原因。然而，IL-27 在流感后继发性肺炎球菌肺炎发病机制中的作用尚不清楚。我们现在报告称，流感感染以 I 型 IFN-α/β受体（IFNAR）信号依赖性方式诱导肺部 IL-27 的产生，这使得小鼠对 IFNAR 途径下游的继发性肺炎球菌感染敏感。缺乏 IL-27 受体的小鼠对继发性肺炎球菌感染具有抗性，并产生更多产生 IL-17A 的 γδ T 细胞，但不是 αβ T 细胞，从而导致宿主防御的早期阶段增强中性粒细胞反应。IL-27 治疗可抑制由肺炎链球菌和树突状细胞激活的产生 IL-17A 的 γδ T 细胞的发育。IL-27 对 γδ T 细胞的这种抑制作用依赖于转录因子 STAT1。最后，中和 IL-27 或给予 IL-17A 恢复了 γδ T 细胞在对抗继发性肺炎球菌感染中的作用。我们的研究定义了我们认为的 IL-27 在削弱宿主对肺炎球菌感染的固有免疫中的新作用。
