title: Novel protective mechanism for interleukin-33 at the mucosal barrier during influenza-associated bacterial superinfection.
abstract: Influenza A is a highly contagious respiratory virus that causes seasonal epidemics and occasional worldwide pandemics. The primary cause of influenza-related mortality is bacterial superinfection. There are numerous mechanisms by which preceding influenza infection attenuates host defense, allowing for increased susceptibility to bacterial pneumonia. Herein, we demonstrate that influenza inhibits Staphylococcus aureus-induced production of interleukin-33 (IL-33). Restoration of IL-33 during influenza A and methicillin-resistant S. aureus superinfection enhanced bacterial clearance and improved mortality. Innate lymphoid Type 2 cells and alternatively activated macrophages are not required for IL-33-mediated protection during superinfection. We show that IL-33 treatment resulted in neutrophil recruitment to the lung, associated with improved bacterial clearance. These findings identify a novel role for IL-33 in antibacterial host defense at the mucosal barrier.
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Robinson
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ramanan
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.|School of Graduate and Advanced Studies, Dartmouth College, Hanover, New Hampshire, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Clay
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: K J
authors.initials: KJ
authors.lastname: McHugh
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Rich
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Alcorn
mesh_terms: D000818:Animals; D058491:Bacterial Load; D007113:Immunity, Innate; D009980:Influenza A virus / Q000276:immunology*; D000067596:Interleukin-33 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D015163:Superinfection; D018418:Th2 Cells / Q000276:immunology
chemical_list: D000067596:Interleukin-33