Establishment of an immune model of infection in aged mice
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(1. Shanghai public health clinical center, Fudan university, Shanghai 201508, China; 2. Institutes of Biomedical Sciences, Fudan university, Shanghai 200032)

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R-33

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    Abstract:

    Objective The immune function of older people decreases with increasing age, while immunosenescence confers increased susceptibility to influenza. After infection, the clinical symptoms of elderly patients are particularly serious, associated with a poor prognosis. Therefore, an aged mouse model that reflects clinically severe influenza virus infection should be established to evaluate the immune responses upon elderly host infection. Methods For this purpose, aged C57 mice (18 -24 months old) were infected with influenza viruses with different levels of virulence, H7N9 (high pathogenicity) and H9N2 (low pathogenicity). We analyzed the weight change and survival after infection. We also dynamically detected viral replication, expression of inflammatory factors, and pathological damage of lung. Results In contrast to adult mice (6 -8 weeks), aged mice lost 30% of their body weight 7 days after infection with H9N2 (adult controls lost only 10%), and the survival rate was reduced to 50% (that of the adult controls was 100%).H9N2 virus replication in the lung of aged mice was higher ( P < 0. 01) and peaked (RNA virus copy number in each gram of lung reached 3. 2 ×10 4 ) on the second day after infection. Inflammatory cytokines (IL?6) and chemokines (MCP?1) were excessively expressed and associated with inflammation in the aged lung, at levels 100 to 1000 times those in the adult control. Lung injury of aged mice was more severe and the repair time after infection was longer. Conclusions We successfully established a model of aged mouse infection. This can reproduce the immune responses in clinical infection, such as infection survival, lung virus replication, and inflammation injury. This model could be important for understanding the mechanism of aging host infection or for evaluating anti?infective drugs.

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History
  • Received:April 26,2018
  • Revised:
  • Adopted:
  • Online: November 15,2018
  • Published: