The H7N9 in uenza A virus infection results in lethal in ammation in the mammalian host via the NLRP3-caspase-1 in ammasome
The H7N9 in uenza A virus infection results in lethal in ammation in the mammalian host via the NLRP3-caspase-1 in ammasome
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DOI：
10.1038/s41598-017-07384-5
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Guangxun Meng
中科院分区：
文献类型：
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作者：
Rongrong Ren;Shuxian Wu;Jialin Cai;Yuqin Yang;Xiaonan Ren;Yanling Feng;Lixiang Chen;Boyin Qin;Chunhua Xu;Hua Yang;Zhigang Song;Di Tian;Yunwen Hu;Xiaohui Zhou;Guangxun Meng
The avian origin in uenza A virus (IAV) H7N9 has caused a considerable number of human infections associated with high rates of death since its emergence in 2013. As a vital component of the host innate immune system, the nucleotide-binding domain leucine-rich repeat containing receptor, pyrin domain containing 3 (NLRP3) in ammasome plays a critical role against H1N1 viral infection. However, the function of NLRP3 in ammasome in host immunological responses to the lethal H7N9 virus is still obscure. Here, we demonstrated that mice de cient for NLRP3 in ammasome components, including NLRP3, caspase-1, and Apoptosis-associated speck-like protein containing a CARD (ASC), were less susceptible to H7N9 viral challenge than wild type (WT) controls. In ammasome de ciency in these animals led to signi cantly milder mortality and less pulmonary in ammation compared with WT mice. Furthermore, IL-1 receptor de cient mice also exhibited a higher survival rate than WT controls. Thus, our study reveals that the NLRP3 in ammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming in ammatory response via caspase-1 activation and associated IL-1 signal. Therefore, ne-tuning the activity of NLRP3 in ammasome or IL-1 signaling may be bene cial for the host to control H7N9 associated lethal pathogenesis.
