title: Critical role of natural killer cells in lung immunopathology during influenza infection in mice.
abstract: Influenza viral infection results in excessive pulmonary inflammation that has been linked to the damage caused by immune responses and viral replication. The multifunctional cytokine interleukin (IL-15), influences the proliferation and maintenance of immune cells such as CD8(+) T cells and natural killer (NK) cells. Here we show that IL-15(-/-) mice are protected from lethal influenza infection. Irrespective of the mouse strains, the protection observed was linked to the lack of NK cells. Increased survival in the IL-15(-/-) or NK1.1(+) cell-depleted wild-type mice was associated with significantly lower lung lesions as well as decreased mononuclear cells and neutrophils in the airway lumen. Levels of interleukin 10 were significantly higher and levels of proinflammatory cytokines, including interleukin 6 and interleukin 12, were significantly lower in the bronchoalveolar lavage fluid from IL-15(-/-) and NK1.1(+) cell-depleted wild-type mice than in that from control mice. Our data suggest that NK cells significantly augment pulmonary inflammation, contributing to the pathogenesis of influenza infection.
authors.affiliation: McMaster Immunology Research Centre and Institute for Infectious Diseases Research, Department of Pathology and Molecular Medicine,  McMaster University Health Sciences Center, Hamilton, Ontario,  Canada.
authors.forename: Mohamed F
authors.initials: MF
authors.lastname: Abdul-Careem
authors.forename: M Firoz
authors.initials: MF
authors.lastname: Mian
authors.forename: Geoffry
authors.initials: G
authors.lastname: Yue
authors.forename: Amy
authors.initials: A
authors.lastname: Gillgrass
authors.forename: Meghan J
authors.initials: MJ
authors.lastname: Chenoweth
authors.forename: Nicole G
authors.initials: NG
authors.lastname: Barra
authors.forename: Marianne V
authors.initials: MV
authors.lastname: Chew
authors.forename: Tiffany
authors.initials: T
authors.lastname: Chan
authors.forename: Amal A
authors.initials: AA
authors.lastname: Al-Garawi
authors.forename: Manel
authors.initials: M
authors.lastname: Jordana
authors.forename: Ali A
authors.initials: AA
authors.lastname: Ashkar
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D049109:Cell Proliferation; D019409:Interleukin-15 / Q000378:metabolism; D007694:Killer Cells, Natural / Q000502:physiology*; D008168:Lung / Q000166:cytology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009975:Orthomyxoviridae / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D019409:Interleukin-15