Interleukin-18 improves the early defence system against influenza virus infection by augmenting natural killer cell-mediated cytotoxicity.
The role of interleukin (IL)-18 in the development of the host defence system against influenza virus infection was investigated. IL-18-deficient (IL-18(-/-)) C57BL/6 mice that were inoculated intranasally with the mouse-adapted strain of human influenza A/PR/8/34 (H1N1) virus showed an increased mortality with the occurrence of pathogenic changes in the lung for the first 3 days of infection, which included pronounced virus growth with massive infiltration of inflammatory cells and elevated nitric oxide production. The interferon-gamma (IFN-gamma) level induced in the respiratory tract of IL-18(-/-) mice in the first few days after virus infection was significantly lower but, in contrast, the IL-12 level was slightly higher than the corresponding levels in wild-type C57BL/6 mice. Natural killer (NK) cell-mediated cytotoxicity in the lung of IL-18(-/-) mice was poorly activated. Local immune responses in the lung such as specific cytotoxic T lymphocyte and antibody production were induced upon influenza virus infection equally well in both strains of mice. These results indicate that IL-18 is involved in controlling influenza virus replication in the lung, especially at an early stage of infection, through activation of the innate immune mechanisms such as IFN and NK cells.
Liu
Beixing
B
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Mori
Isamu
I
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Hossain
Md Jaber
MJ
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Dong
Li
L
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
Takeda
Kiyoshi
K
Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
Kimura
Yoshinobu
Y
Department of Microbiology, Fukui Medical University School of Medicine, Shimoaisuki 23-3, Matsuoka-cho, Yoshida-gun, Fukui 910-1193, Japan.
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D009980:Influenza A virus; D007371:Interferon-gamma / Q000032:analysis; D018664:Interleukin-12 / Q000032:analysis; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D011014:Pneumonia / Q000276:immunology; D012137:Respiratory System / Q000276:immunology
D020382:Interleukin-18; D018664:Interleukin-12; D009569:Nitric Oxide; D007371:Interferon-gamma