Effect of a cytokine storm on immune responses against viral 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 A cytokine storm occurs during infection by highly pathogenic viruses such as avian influenza virus. Higher levels of inflammatory responses are more commonly observed in the elderly, associated with worse clinical outcomes. In this study, we investigated the effect of inflammatory responses on the immune response against viral infection in the lung of aged mice. Methods Aged mice (18 -24 months old) were infected with influenza virus H9N2 to establish an infection model. Adult mice (6 - 8 weeks old) were used as the control. After infection, we quantitatively analyzed the expression of inflammatory cytokines in the lung and periphery blood. During the acute infection, murine lung tissues were collected and subjected to in situ analysis of the distribution of recruited immune cells by immunohistochemistry, and pulmonary T cells were counted among digested single cells of lung tissue. Results Compared with the adult mice infected with H9N2, aged mice showed significant weight loss and a low survival rate of 50%.Inflammatory cytokines were rarely detected in the infected adult mice, but were highly detected in the lungs of aged mice.Among them, IL-6 and chemokine MCP-1 were significantly high, which reached peaks of more than 4000 pg/ mL and were 100 - 1000 times higher than those in the adult control mice at day 2 post-infection. Additionally, the pulmonary macrophage response and migration of neutrophils were weaker. On day 7 post-infection, the number of CD8 + T cells decreased significantly in the aged lung, while the number and proportion of CD4 + T cells remained normal. Conclusions An inflammatory cytokine storm is found in the lung of aged mice infected with low pathogenic influenza virus H9N2.Compared with adult mice, the migration ability of immune cells is decreased, and the acquired cellular immunity intensity is reduced significantly.

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History
  • Received:April 26,2018
  • Revised:
  • Adopted:
  • Online: January 08,2019
  • Published: