title: Antimicrobial peptides alter early immune response to influenza A virus infection in C57BL/6 mice.
abstract: Influenza is a disease of the respiratory system caused by single stranded RNA viruses with varying genotypes. Immunopathogenesis to influenza viruses differs based on virus strain, dose, and mouse strain used in laboratory models. Although effective mucosal immune defenses are important in early host defense against influenza, information on the kinetics of these immune defense mechanisms during the course of influenza infection is limited. We investigated changes to antimicrobial peptides and primary innate immune cells at early time points after infection and compared these variables between two prominent H1N1 influenza A virus (IAV) strains, A/CA/04/2009 and A/PR/08/1934 in C57BL/6 mice. Alveolar and parenchymal macrophage ratios were altered after IAV infection and pro-inflammatory cytokine production in macrophages was induced after IAV infection. Genes encoding antimicrobial peptides, β-defensin (Defb4), bactericidal-permeability increasing protein (Bpifa1), and cathelicidin antimicrobial peptide (Camp), were differentially regulated after IAV infection and the kinetics of Defb4 expression differed in response to each virus strain. Beta-defensin reduced infectivity of A/CA/04/2009 virus but not A/PR/08/1934. Beta defensins also changed the innate immune cell profile wherein mice pre-treated with β-defensin had increased alveolar macrophages and CD103(+) dendritic cells, and reduced CD11b(+) dendritic cells and neutrophils. In addition to highlighting that immune responses may vary based on influenza virus strain used, our data suggest an important role for antimicrobial peptides in host defense against influenza virus.
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
authors.forename: Kim S
authors.initials: KS
authors.lastname: LeMessurier
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38103, USA; Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: asamaras@uthsc.edu.
authors.forename: Amali E
authors.initials: AE
authors.lastname: Samarasinghe
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D054884:Host-Pathogen Interactions / Q000187:drug effects* / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects*; D009980:Influenza A virus / Q000187:drug effects / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D012137:Respiratory System / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014779:Virus Replication; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D023181:Antimicrobial Cationic Peptides; D023083:beta-Defensins
keywords: Defensins; Dendritic cell; H1N1 influenza; Inflammation; Macrophage