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

Cytokine. 2016 May:81:23-7. doi: 10.1016/j.cyto.2016.01.016. Epub 2016 Feb 5.

Abstract

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.

Keywords: IL-35; Immune response; Infection; Influenza; Pneumonia; Streptococcus pneumoniae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Coinfection / complications
  • Coinfection / metabolism*
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Host-Pathogen Interactions
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology
  • 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, Pneumococcal / complications
  • Pneumonia, Pneumococcal / metabolism*
  • Receptors, Cytokine / genetics
  • Receptors, Cytokine / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation

Substances

  • EBI3 protein, human
  • Ebi3 protein, mouse
  • Interleukin-12 Subunit p35
  • Interleukins
  • Minor Histocompatibility Antigens
  • Receptors, Cytokine
  • interleukin-35, human
  • interleukin-35, mouse