Natural killer T (NKT) cell activation is responsible for eliminating pathogens. However, the biological functions of NKT cells against influenza virus are not fully understood. We therefore investigated the effects of NKT cells in viral infection using CD1d knockout (KO) mice. When CD1d KO or wild-type (WT) mice were infected with a sub-lethal dosage of the influenza virus, the survival rate of CD1d KO mice was significantly lower than for WT mice in association with delayed viral clearance in the lungs. Consistently, IFN-γ production in bronchoalveolar lavage fluid of CD1d KO mice was largely reduced compared to WT mice during infection. Moreover, the cytotoxic activities of NK cells and viral antigen-specific CD8(+) T cells were impaired in CD1d KO mice. It was concluded that activated NKT cell-induced IFN-γ release enhances both NK-cell activity and antigen-specific CD8(+) T cells to eliminate the influenza virus, thus leading to an enhanced survival.

PurposeThis study was conducted in order to investigate whether the virulence of the influenza virus infection is affected by asthma in mice.MethodsMice 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.ResultsWhen 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.ConclusionNK 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.

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