Interleukin-35 is upregulated in response to influenza virus infection and secondary bacterial pneumonia

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2016-05, Vol.81, p.23-27
• Main Authors: Chen, Yi, Wang, Chuan-jiang, Lin, Shi-hui, Zhang, Mu, Li, Sheng-yuan, Xu, Fang
• Format: Article
• Language: English
• Subjects: Animals; Bacteria; Cells, Cultured; Coinfection - complications; Coinfection - metabolism; Dogs; Enzyme-Linked Immunosorbent Assay; Host-Pathogen Interactions; Humans; IL-35; Immune response; Infection; Influenza; Influenza A Virus, H1N1 Subtype - physiology; Influenza virus; Influenza, Human - metabolism; Influenza, Human - virology; Interleukin-12 Subunit p35 - genetics; Interleukin-12 Subunit p35 - metabolism; Interleukins - genetics; Interleukins - metabolism; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - virology; Lung - metabolism; Lung - microbiology; Lung - virology; Madin Darby Canine Kidney Cells; Mice, Inbred C57BL; Mice, Knockout; Minor Histocompatibility Antigens - genetics; Minor Histocompatibility Antigens - metabolism; Orthomyxoviridae Infections - complications; Orthomyxoviridae Infections - metabolism; Orthomyxoviridae Infections - virology; Pneumonia; Pneumonia, Pneumococcal - complications; Pneumonia, Pneumococcal - metabolism; Receptors, Cytokine - genetics; Receptors, Cytokine - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Streptococcus pneumoniae; Up-Regulation
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2016.01.016

•We developed a murine model of postinfluenza pneumococcal pneumonia.•We collected Serum sample from 30 healthy individuals and 33 patients.•We found elevated pulmonary IL-35 induced by influenza infection following secondary pneumococcal infection. Postinfluenza pneumococcal pneumonia is an important cause of global morbidity and mortality. What causes this increased susceptibility is not well elucidated. IL-35 is a newly described cytokine in infectious tolerance. A murine model was established to study postinfluenza pneumococcal pneumonia and evaluate the role of IL-35 in host defense against postinfluenza pneumococcal pneumonia. Pulmonary IL-35 was rapidly up-regulated during murine influenza infection, which was partially mediated by type I IFN-α/β receptor signaling pathway. Secondary pneumococcal infection led to a synergistic IL-35 response in influenza-infected mice. Clinical analysis showed that IL-35 levels were significantly elevated in the patients with influenza infection compared with healthy individuals and influenza infection could induce IL-35 production from human peripheral blood mononuclear cells. These data suggest that IL-35 contributes to the increased susceptibility to secondary pneumococcal pneumonia at least in part by inhibiting the early immune response.