Activation of IL-27 signalling promotes development of postinfluenza pneumococcal pneumonia.

Activation of IL-27 signalling promotes development of postinfluenza pneumococcal pneumonia.
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IL-27信号传导的激活促进流感后肺炎球菌肺炎的发展

DOI:
10.1002/emmm.201302890
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发表时间:
2014-01
影响因子:
11.1
通讯作者:
Yin, Yibing
Yin, Yibing
中科院分区:
医学1区
文献类型:
--
作者:
Cao, Ju;Wang, Dongsheng;Xu, Fang;Gong, Yi;Wang, Hong;Song, Zixin;Li, Dageng;Zhang, Hua;Li, Dairong;Zhang, Liping;Xia, Yun;Xu, Huajian;Lai, Xaiofei;Lin, Shihui;Zhang, Xuemei;Ren, Guosheng;Dai, Yubing;Yin, Yibing

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流感后肺炎球菌肺炎是人类死亡的常见原因。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。我们现在报道,流感感染以I型IFN-α/β受体(IFNAR)信号传导依赖的方式诱导肺IL-27产生,这使小鼠对IFNAR途径下游的继发性肺炎球菌感染敏感。IL-27受体缺陷的小鼠对继发性肺炎球菌感染具有抗性,并产生更多的IL-17 A产生γδ T细胞,但不产生αβ T细胞,从而导致在宿主防御的早期阶段增强的中性粒细胞反应。IL-27处理可抑制肺炎链球菌和树突状细胞激活的产生IL-17 A的γδ T细胞的发育。IL-27对γδ T细胞的这种抑制活性依赖于转录因子STAT 1。最后,中和IL-27或给予IL-17 A恢复了γδ T细胞在对抗继发性肺炎球菌感染中的作用。我们的研究确定了我们认为IL-27在损害宿主对肺炎球菌感染的先天免疫中的新作用。
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.
DOI: 10.1016/s1473-3099(06)70466-2
发表时间: 2006-05
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影响因子: --
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Brundage JF
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