Critical Role of Natural Killer Cells in Lung Immunopathology During Influenza Infection in Mice

• Published in: The Journal of infectious diseases Vol. 206; no. 2; pp. 167 - 177
• Main Authors: Abdul-Careem, Mohamed F., Mian, M. Firoz, Yue, Geoffry, Gillgrass, Amy, Chenoweth, Meghan J., Barra, Nicole G., Chew, Marianne V., Chan, Tiffany, Al-Garawi, Amal A., Jordana, Manel, Ashkar, Ali A.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.07.2012
• Subjects: Animals; Biological and medical sciences; Body weight; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Cell Proliferation; Cytokines; Fundamental and applied biological sciences. Psychology; Infections; Infectious diseases; Interleukin-15 - metabolism; Interleukins; Killer Cells, Natural - physiology; Lung - cytology; Lung - pathology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Microbiology; Natural killer cells; Natural killer T cells; Orthomyxoviridae; Orthomyxoviridae - immunology; Orthomyxoviridae Infections - pathology; Pathology; Signal Transduction; T lymphocytes; Viruses; Natural killer cell; Infection; Vertebrata; Mammalia; Mouse; Viral disease; Influenza; Lung; Rodentia; Respiratory system
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jis340

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.