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.
Copyright © 2016 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cells, Cultured
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Coinfection / complications
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Coinfection / metabolism*
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Dogs
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Enzyme-Linked Immunosorbent Assay
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Host-Pathogen Interactions
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Humans
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Influenza A Virus, H1N1 Subtype / physiology
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Influenza, Human / metabolism
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Influenza, Human / virology
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Interleukin-12 Subunit p35 / genetics
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Interleukin-12 Subunit p35 / metabolism
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Interleukins / genetics
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Interleukins / metabolism*
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Leukocytes, Mononuclear / metabolism
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Leukocytes, Mononuclear / virology
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Lung / metabolism*
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Lung / microbiology
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Lung / virology
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Madin Darby Canine Kidney Cells
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Mice, Inbred C57BL
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Mice, Knockout
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Minor Histocompatibility Antigens / genetics
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Minor Histocompatibility Antigens / metabolism
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Orthomyxoviridae Infections / complications
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Orthomyxoviridae Infections / metabolism*
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Orthomyxoviridae Infections / virology
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Pneumonia, Pneumococcal / complications
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Pneumonia, Pneumococcal / metabolism*
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Receptors, Cytokine / genetics
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Receptors, Cytokine / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Up-Regulation
Substances
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EBI3 protein, human
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Ebi3 protein, mouse
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Interleukin-12 Subunit p35
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Interleukins
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Minor Histocompatibility Antigens
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Receptors, Cytokine
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interleukin-35, human
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interleukin-35, mouse