Abstract
The 2009 flu pandemic involved the emergence of a new strain of a swine-origin H1N1 influenza virus (S-OIV H1N1) that infected almost every country in the world. Most infections resulted in respiratory illness and some severe cases resulted in acute lung injury. In this report, we are the first to describe a mouse model of S-OIV virus infection with acute lung injury and immune responses that reflect human clinical disease. The clinical efficacy of the antiviral oseltamivir (Tamiflu) administered in the early stages of S-OIV H1N1 infection was confirmed in the mouse model. Moreover, elevated levels of IL-17, Th-17 mediators and IL-17-responsive cytokines were found in serum samples of S-OIV-infected patients in Beijing. IL-17 deficiency or treatment with monoclonal antibodies against IL-17-ameliorated acute lung injury induced by the S-OIV H1N1 virus in mice. These results suggest that IL-17 plays an important role in S-OIV-induced acute lung injury and that monoclonal antibodies against IL-17 could be useful as a potential therapeutic remedy for future S-OIV H1N1 pandemics.
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Acknowledgements
We thank Zongsheng Han, Yunli Ling and Ran Zhang for technical support. This work was supported by the National Natural Science Foundation of China (30625013 and 30623009), the Ministry of Science and Technology of China (2009CB522102 and 2009CB522105) and the Ministry of Health (2009ZX10004-308). Dr Zhinan Yin was supported by the National Outstanding Young Scientist Award of National Natural Science Foundation of China (30725015).
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(Supplementary information is linked to the online version of the paper on the Cell Research website.)
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Supplementary information, Table S1
Basic information of patients recruited. (PDF 867 kb)
Supplementary information, Figure S1
Flow chart of S-OIV-infected patient recruitment and sample collection in the hospitals in Beijing. (PDF 495 kb)
Supplementary information, Figure S2
Acute lung injury induced by S-OIV H1N1 in mice is not improved by administration of monoclonal antibodies against TNF-alpha. (PDF 375 kb)
Supplementary information, Figure S3
Monoclonal antibodies against IL-17 do not alter the replication of S-OIV H1N1 in mice. (PDF 510 kb)
Supplementary information, Data S1
Materials and Methods (PDF 127 kb)
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Li, C., Yang, P., Sun, Y. et al. IL-17 response mediates acute lung injury induced by the 2009 Pandemic Influenza A (H1N1) Virus. Cell Res 22, 528–538 (2012). https://doi.org/10.1038/cr.2011.165
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DOI: https://doi.org/10.1038/cr.2011.165
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