title: Immunity to the conserved influenza nucleoprotein reduces susceptibility to secondary bacterial infections.
abstract: Influenza causes >250,000 deaths annually in the industrialized world, and bacterial infections frequently cause secondary illnesses during influenza outbreaks, including pneumonia, bronchitis, sinusitis, and otitis media. In this study, we demonstrate that cross-reactive immunity to mismatched influenza strains can reduce susceptibility to secondary bacterial infections, even though this fails to prevent influenza infection. Specifically, infecting mice with H3N2 influenza before challenging with mismatched H1N1 influenza reduces susceptibility to either Gram-positive Streptococcus pneumoniae or Gram-negative Klebsiella pneumoniae. Vaccinating mice with the highly conserved nucleoprotein of influenza also reduces H1N1-induced susceptibility to lethal bacterial infections. Both T cells and Abs contribute to defense against influenza-induced bacterial diseases; influenza cross-reactive T cells reduce viral titers, whereas Abs to nucleoprotein suppress induction of inflammation in the lung. These findings suggest that nonneutralizing influenza vaccines that fail to prevent influenza infection may nevertheless protect the public from secondary bacterial diseases when neutralizing vaccines are not available.
authors.affiliation: Trudeau Institute, Saranac Lake, NY 12983, USA. lhaynes@trudeauinstitute.org
authors.forename: Laura
authors.initials: L
authors.lastname: Haynes
authors.forename: Frank M
authors.initials: FM
authors.lastname: Szaba
authors.forename: Sheri M
authors.initials: SM
authors.lastname: Eaton
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Kummer
authors.forename: Paula A
authors.initials: PA
authors.lastname: Lanthier
authors.forename: Ashlee H
authors.initials: AH
authors.lastname: Petell
authors.forename: Debra K
authors.initials: DK
authors.lastname: Duso
authors.forename: Deyan
authors.initials: D
authors.lastname: Luo
authors.forename: Jr-Shiuan
authors.initials: JS
authors.lastname: Lin
authors.forename: Julie S
authors.initials: JS
authors.lastname: Lefebvre
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Johnson
authors.forename: Jacob E
authors.initials: JE
authors.lastname: Kohlmeier
authors.forename: David L
authors.initials: DL
authors.lastname: Woodland
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Smiley
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D003429:Cross Reactions; D004198:Disease Susceptibility / Q000276:immunology / Q000382:microbiology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000382:microbiology; D007710:Klebsiella Infections / Q000276:immunology*; D007711:Klebsiella pneumoniae / Q000276:immunology*; D051379:Mice; D019590:Nucleocapsid Proteins / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D019590:Nucleocapsid Proteins