Source:International Immunopharmacology, Volume 59
Author(s): Nianping Song, Pei Li, Yuting Jiang, Hong Sun, Jing Cui, Guangyu Zhao, Dan Li, Yan Guo, Yuehong Chen, Jimin Gao, Shihui Sun, Yusen Zhou
Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). C5aR1-deficient mice and mice treated with an anti-C5aR1 antibody were used as models to study the C5a-C5aR1 axis during acute lung injury (ALI) induced by influenza virus infection. The results showed that blocking the C5a-C5aR1 axis alleviated ALI by inhibiting endothelial cell activation and dampening the host immune response (i.e., reduced TNF-α, IL-1β, IL-6, IP-10, MCP-1, IL-12p70, and IFN-γ concentrations in plasma), particularly CTL-mediated immunopathology. Furthermore, blockade of the C5a-C5aR1 axis inhibited viral replication in lung tissue. Taken together, the results indicate that the C5a-C5aR1 axis plays an important role in the outcome of ALI induced by influenza virus infection and that regulation of complement activation, particularly the C5aR1 inhibition, is a promising intervention and adjunctive treatment.
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