title: IL-15 participates in the respiratory innate immune response to influenza virus infection.
abstract: Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention.
authors.affiliation: Department of Cellular Biology, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Katherine C
authors.initials: KC
authors.lastname: Verbist
authors.forename: David L
authors.initials: DL
authors.lastname: Rose
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Cole
authors.forename: Mary B
authors.initials: MB
authors.lastname: Field
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Klonowski
mesh_terms: D000818:Animals; D018893:Bronchoalveolar Lavage; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D019409:Interleukin-15 / Q000276:immunology* / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D012137:Respiratory System / Q000276:immunology* / Q000821:virology
chemical_list: D019409:Interleukin-15