Mice with Asthma Are More Resistant to Influenza Virus Infection and NK Cells Activated by the Induction of Asthma Have Potentially Protective Effects

• Published in: Journal of clinical immunology 2012-04, Vol.32 (2), p.256-267
• Main Authors: Ishikawa, Hiroki, Sasaki, Hiraku, Fukui, Toshie, Fujita, Koji, Kutsukake, Etsuko, Matsumoto, Tetsuya
• Format: Article
• Language: English
• Subjects: Alveoli; Animals; Antibody Specificity; Antiviral agents; Asthma; Asthma - complications; Asthma - immunology; Asthma - mortality; Biomedical and Life Sciences; Biomedicine; Body weight; Body weight loss; Bronchoalveolar Lavage Fluid - cytology; Bronchoalveolar Lavage Fluid - immunology; Bronchus; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell Movement - immunology; Cell survival; Cytokines; Cytokines - biosynthesis; Cytotoxicity; Cytotoxicity, Immunologic; Disease Susceptibility - immunology; Female; Immunoglobulin E - blood; Immunoglobulin E - immunology; Immunology; Infection; Infectious Diseases; Influenza; Influenza virus; Interferon-gamma - biosynthesis; Internal Medicine; Killer Cells, Natural - immunology; Lung - immunology; Lymphocyte Activation - immunology; Lymphocytes T; Medical Microbiology; Mice; Mice, Inbred C57BL; Morbidity; Mortality; Natural killer cells; Orthomyxoviridae Infections - complications; Orthomyxoviridae Infections - immunology; Orthomyxoviridae Infections - prevention & control; Remission; Spleen - immunology; Virulence
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-011-9619-2

Purpose This study was conducted in order to investigate whether the virulence of the influenza virus infection is affected by asthma in mice. Methods Mice with asthma or control mice were infected with influenza virus. The survival rate, body weight, virus titer, cytokine profile, and cell infiltration in bronchoalveolar lavage fluid (BALF) were measured. The NK cell cytotoxicity was determined by a co-culture system with YAC-1 cells, and the effects of NK cells were observed by depletion of NK cells using anti-asialoGM1 serum. The virus-specific CD8 + T cell killing assay was also performed. Results When asthmatic or control mice were infected with non- and sub-lethal doses of influenza virus, the asthmatic mice were more resistant to the virus than control mice with regard to the survival rate, the remission of body weight loss, and the virus burden. Anti-viral cytokines and the NK cell number were increased in the BALF of asthmatic mice before the infection. The NK cell cytotoxicity in the asthmatic mice was significantly enhanced compared to that in control mice, and the depletion of NK cells in asthmatic mice was abrogated both the improved survival rate and the recovery of the body weight loss. The antigen-specific CD8 + T cell killing activity in asthmatic mice was also significantly increased following the infection compared to that in control mice. Conclusion NK cell activated by the induction of asthma and the subsequently activated antigen-specific CD8 + T cells could promptly eliminate the viral-infected cells, thus leading to improvements in the morbidity and mortality of influenza virus infection.