tetano
Editor, Senior Moderator
Sci Rep. 2017 Aug 8;7(1):7625. doi: 10.1038/s41598-017-07384-5.
[h=1]The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome.[/h] Ren R[SUP]1[/SUP], Wu S[SUP]2[/SUP], Cai J[SUP]3[/SUP], Yang Y[SUP]4[/SUP], Ren X[SUP]1[/SUP], Feng Y[SUP]1[/SUP], Chen L[SUP]1[/SUP], Qin B[SUP]1[/SUP], Xu C[SUP]1[/SUP], Yang H[SUP]1[/SUP], Song Z[SUP]1[/SUP], Tian D[SUP]1[/SUP], Hu Y[SUP]1,[/SUP][SUP]5[/SUP], Zhou X[SUP]6,[/SUP][SUP]7[/SUP], Meng G[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The avian origin influenza 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) inflammasome plays a critical role against H1N1 viral infection. However, the function of NLRP3 inflammasome in host immunological responses to the lethal H7N9 virus is still obscure. Here, we demonstrated that mice deficient for NLRP3 inflammasome 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. Inflammasome deficiency in these animals led to significantly milder mortality and less pulmonary inflammation compared with WT mice. Furthermore, IL-1 receptor deficient mice also exhibited a higher survival rate than WT controls. Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal. Therefore, fine-tuning the activity of NLRP3 inflammasome or IL-1 signaling may be beneficial for the host to control H7N9 associated lethal pathogenesis.
PMID: 28790324 PMCID: PMC5548739 DOI: 10.1038/s41598-017-07384-5
Free PMC Article
[h=1]The H7N9 influenza A virus infection results in lethal inflammation in the mammalian host via the NLRP3-caspase-1 inflammasome.[/h] Ren R[SUP]1[/SUP], Wu S[SUP]2[/SUP], Cai J[SUP]3[/SUP], Yang Y[SUP]4[/SUP], Ren X[SUP]1[/SUP], Feng Y[SUP]1[/SUP], Chen L[SUP]1[/SUP], Qin B[SUP]1[/SUP], Xu C[SUP]1[/SUP], Yang H[SUP]1[/SUP], Song Z[SUP]1[/SUP], Tian D[SUP]1[/SUP], Hu Y[SUP]1,[/SUP][SUP]5[/SUP], Zhou X[SUP]6,[/SUP][SUP]7[/SUP], Meng G[SUP]8[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The avian origin influenza 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) inflammasome plays a critical role against H1N1 viral infection. However, the function of NLRP3 inflammasome in host immunological responses to the lethal H7N9 virus is still obscure. Here, we demonstrated that mice deficient for NLRP3 inflammasome 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. Inflammasome deficiency in these animals led to significantly milder mortality and less pulmonary inflammation compared with WT mice. Furthermore, IL-1 receptor deficient mice also exhibited a higher survival rate than WT controls. Thus, our study reveals that the NLRP3 inflammasome is deleterious for the host during H7N9 infection in mice, which is due to an overwhelming inflammatory response via caspase-1 activation and associated IL-1 signal. Therefore, fine-tuning the activity of NLRP3 inflammasome or IL-1 signaling may be beneficial for the host to control H7N9 associated lethal pathogenesis.
PMID: 28790324 PMCID: PMC5548739 DOI: 10.1038/s41598-017-07384-5
Free PMC Article