title: Activation of IL-27 signalling promotes development of postinfluenza pneumococcal pneumonia.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Cao
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Gong
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Zixin
authors.initials: Z
authors.lastname: Song
authors.forename: Dageng
authors.initials: D
authors.lastname: Li
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Dairong
authors.initials: D
authors.lastname: Li
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Xia
authors.forename: Huajian
authors.initials: H
authors.lastname: Xu
authors.forename: Xaiofei
authors.initials: X
authors.lastname: Lai
authors.forename: Shihui
authors.initials: S
authors.lastname: Lin
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.forename: Guosheng
authors.initials: G
authors.lastname: Ren
authors.forename: Yubing
authors.initials: Y
authors.lastname: Dai
authors.forename: Yibing
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D064094:Interleukin-27 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000821:virology; D011018:Pneumonia, Pneumococcal / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality; D018121:Receptors, Cytokine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000502:physiology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology
chemical_list: D057134:Antibodies, Neutralizing; C484747:Il27ra protein, mouse; D020381:Interleukin-17; D064094:Interleukin-27; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D050794:STAT1 Transcription Factor