title: Influenza virus infection causes neutrophil dysfunction through reduced G-CSF production and an increased risk of secondary bacteria infection in the lung.
abstract: The immunological mechanisms of secondary bacterial infection followed by influenza virus infection were examined. When mice were intranasally infected with influenza virus A and then infected with P. aeruginosa at 4 days after viral infection, bacterial clearance in the lung significantly decreased compared to that of non-viral infected mice. Neutrophils from viral infected mice showed impaired digestion and/or killing of phagocytized bacteria due to reduced myeloperoxidase (MPO) activity. G-CSF production in the lungs of viral infected mice was lower than that of non-viral infected mice after secondary bacterial infection. When viral infected mice were injected with G-CSF before secondary bacterial infection, the MPO activity of viral infected mice restored to the same level as that of non-infected mice. Bacteria clearance in viral infected mice was also recovered by G-CSF administration. Thus, neutrophil dysfunction caused by influenza virus is attributed to insufficient G-CSF production, which induces a secondary bacterial infection.
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Department of Microbiology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan.
authors.forename: Toshie
authors.initials: T
authors.lastname: Fukui
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ino
authors.affiliation: Department of Health Science, School of Health and Sports Science, Juntendo University, Inzai, Chiba 270-1695, Japan.
authors.forename: Hiraku
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Microbiology, Tokyo Medical University, Shinjuku-ku, Tokyo 160-8402, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Awano
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Kohda
authors.affiliation: Department of Microbiology and Immunology, Showa University School of Medicine, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: k-tanaka@med.showa-u.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D058491:Bacterial Load; D060085:Coinfection; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000096:biosynthesis*; D018836:Inflammation Mediators / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D009976:Orthomyxoviridae Infections / Q000150:complications / Q000276:immunology* / Q000378:metabolism* / Q000821:virology; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000209:etiology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology; D012306:Risk
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016179:Granulocyte Colony-Stimulating Factor; D009195:Peroxidase
keywords: G-CSF; Influenza virus; Neutrophil; P. aeruginosa