Activation of IL-27 signalling promotes development of postinfluenza pneumococcal pneumonia
Version of Record online: 29 OCT 2013
© 2013 The Authors.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
EMBO Molecular Medicine
Volume 6, Issue 1, pages 120–140, January 2014
How to Cite
Cao, J., Wang, D., Xu, F., Gong, Y., Wang, H., Song, Z., Li, D., Zhang, H., Li, D., Zhang, L., Xia, Y., Xu, H., Lai, X., Lin, S., Zhang, X., Ren, G., Dai, Y. and Yin, Y. (2014), Activation of IL-27 signalling promotes development of postinfluenza pneumococcal pneumonia. EMBO Mol Med, 6: 120–140. doi: 10.1002/emmm.201302890
- Issue online: 9 JAN 2014
- Version of Record online: 29 OCT 2013
- Manuscript Revised: 19 SEP 2013
- Manuscript Accepted: 19 SEP 2013
- Manuscript Received: 12 APR 2013
- National Natural Science Foundation of China. Grant Numbers: 81370110, 81000711, 81200054, 81371778
- Natural Science Foundation of Chongqing. Grant Number: 2011BB5139
- First Affiliated Hospital of Chongqing Medical University. Grant Number: 20100305
- influenza virus;
- Streptococcus pneumoniae ;
- γδ T cells
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.
Influenza infection is shown to induce pulmonary IL27 production in an IFNAR-dependent manner, by directly and indirectly suppressing IL17A production by γδ T cells, which result in increased sensitivity to secondary pneumococcal infection in vivo.
- IL-27 expression was up-regulated via IFNAR signaling pathway following influenza infection.
- The development of post-influenza pneumococcal pneumonia was regulated by IL-27.
- Innate IL-17A production from γδ T cells upon pneumococcal infection could be inhibited by IL-27.
- The inhibitory effect of IL-27 on γδ T cells was dependent on STAT1
- Protection against post-influenza pneumococcal pneumonia could be achieved by targeting IL-27.