title: Eosinophils Promote Antiviral Immunity in Mice Infected with Influenza A Virus.
abstract: Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus. The transfer of eosinophils from the lungs of allergen-sensitized and challenged mice into influenza virus-infected mice resulted in reduced morbidity and viral burden, improved lung compliance, and increased CD8+T cell numbers in the airways. In vitro assays with primary or bone marrow-derived eosinophils were used to determine eosinophil responses to the virus using the laboratory strain (A/PR/08/1934) or the pandemic strain (A/CA/04/2009) of IAV. Eosinophils were susceptible to IAV infection and responded by activation, piecemeal degranulation, and upregulation of Ag presentation markers. Virus- or viral peptide-exposed eosinophils induced CD8+T cell proliferation, activation, and effector functions. Our data suggest that eosinophils promote host cellular immunity to reduce influenza virus replication in lungs, thereby providing a novel mechanism by which hosts with allergic asthma may be protected from influenza morbidity.
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103; asamaras@uthsc.edu.|Children's Foundation Research Institute, Memphis, TN 38103.|Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Amali E
authors.identifier: 0000-0002-3104-2823
authors.initials: AE
authors.lastname: Samarasinghe
authors.affiliation: Laboratory of Cellular Biology, Federal University of Juiz de Fora, Juiz de Fora, MG 36036, Brazil.
authors.forename: Rossana C N
authors.identifier: 0000-0003-1736-0806
authors.initials: RC
authors.lastname: Melo
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Susu
authors.initials: S
authors.lastname: Duan
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103.|Children's Foundation Research Institute, Memphis, TN 38103.
authors.forename: Kim S
authors.initials: KS
authors.lastname: LeMessurier
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Swantje
authors.initials: S
authors.lastname: Liedmann
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Sherri L
authors.identifier: 0000-0003-4199-661X
authors.initials: SL
authors.lastname: Surman
authors.affiliation: Department of Biochemistry, Mayo Clinic, Scottsdale, AZ 85259.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Julia L
authors.initials: JL
authors.lastname: Hurwitz
authors.affiliation: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105; and.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Thomas
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103.|Children's Foundation Research Institute, Memphis, TN 38103.|Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
mesh_terms: D000818:Animals; D001249:Asthma / Q000150:complications / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology*; D011657:Pulmonary Eosinophilia / Q000276:immunology