title: Regulation of IFN-γ by IL-13 dictates susceptibility to secondary postinfluenza MRSA pneumonia.
abstract: Superinfection in mice at day 7 postinfluenza infection exacerbates bacterial pneumonia at least in part via downstream effects of increased IFN-γ signaling. Here we show that up to 3 days postinfluenza infection, mice have reduced susceptibility to superinfection with methicillin-resistant Staphylococcus aureus (MRSA), but that superinfection during that time exacerbated influenza disease. This was due to IL-13 signaling that was advantageous for resolving MRSA infection via inhibition of IFN-γ, but was detrimental to the clearance of influenza virus. However, if superinfection did not occur until the near resolution of influenza infection (day 7), IL-13 signaling was inhibited, at least in part by upregulation of IL-13 decoy receptor (IL-13Rα2), which in turn caused increases in IFN-γ signaling and exacerbation of bacterial infection. Understanding these cytokine sequelae is critical to development of immunotherapies for influenza-MRSA coinfection since perturbations of these sequelae at the wrong time could increase susceptibility to MRSA and/or influenza.
authors.affiliation: Department of Microbiology and Immunology, Montana State University, Bozeman, MT, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Rynda-Apple
authors.forename: Ann
authors.initials: A
authors.lastname: Harmsen
authors.forename: Anfin S
authors.initials: AS
authors.lastname: Erickson
authors.forename: Kyle
authors.initials: K
authors.lastname: Larson
authors.forename: Rachelle V
authors.initials: RV
authors.lastname: Morton
authors.forename: Laura E
authors.initials: LE
authors.lastname: Richert
authors.forename: Allen G
authors.initials: AG
authors.lastname: Harmsen
mesh_terms: D000818:Animals; D058491:Bacterial Load; D060085:Coinfection; D004198:Disease Susceptibility; D007371:Interferon-gamma / Q000235:genetics*; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology*; D008168:Lung / Q000382:microbiology / Q000821:virology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D018410:Pneumonia, Bacterial / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000276:immunology*; D015163:Superinfection / Q000276:immunology* / Q000382:microbiology; D019562:Viral Load
chemical_list: D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D011994:Recombinant Proteins; D007371:Interferon-gamma
keywords: IFN-γ ⋅ IL-13 ⋅ Influenza ⋅ Methicillin-resistant Staphylococcus aureus (MRSA) ⋅ Secondary-bacterial infections
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