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.