Department of Microbiology, Tokyo Medical University, 6-1-1 Shinjuku, Shinjuku-ku, Tokyo 160-8402, Japan.
J Clin Immunol. 2012 Apr;32(2):256-67. doi: 10.1007/s10875-011-9619-2. Epub 2011 Dec 2.
This study was conducted in order to investigate whether the virulence of the influenza virus infection is affected by asthma in mice.
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.
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.
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.
本研究旨在探讨哮喘是否会影响流感病毒感染的毒力。
将哮喘小鼠或对照小鼠感染流感病毒。测量存活率、体重、病毒滴度、细胞因子谱和支气管肺泡灌洗液(BALF)中的细胞浸润。通过与 YAC-1 细胞共培养系统测定 NK 细胞细胞毒性,并使用抗-asialoGM1 血清耗尽 NK 细胞观察 NK 细胞的作用。还进行了病毒特异性 CD8(+)T 细胞杀伤测定。
当哮喘或对照小鼠感染非致死和亚致死剂量的流感病毒时,与对照小鼠相比,哮喘小鼠在存活率、体重减轻缓解和病毒载量方面对病毒的抵抗力更强。感染前哮喘小鼠 BALF 中的抗病毒细胞因子和 NK 细胞数量增加。与对照小鼠相比,哮喘小鼠的 NK 细胞细胞毒性明显增强,哮喘小鼠中 NK 细胞的耗竭既改善了存活率,又恢复了体重减轻。感染后哮喘小鼠的抗原特异性 CD8(+)T 细胞杀伤活性也明显高于对照小鼠。
哮喘诱导的 NK 细胞激活和随后激活的抗原特异性 CD8(+)T 细胞可以迅速清除病毒感染的细胞,从而改善流感病毒感染的发病率和死亡率。