tetano
Editor, Senior Moderator
PLoS One. 2019 Feb 22;14(2):e0212236. doi: 10.1371/journal.pone.0212236. eCollection 2019.
[h=1]Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae.[/h] Rodriguez AE[SUP]1[/SUP], Bogart C[SUP]1[/SUP], Gilbert CM[SUP]2[/SUP], McCullers JA[SUP]3[/SUP], Smith AM[SUP]3[/SUP], Kanneganti TD[SUP]4[/SUP], Lupfer CR[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Viral-bacterial coinfections, such as with influenza A virus and Streptococcus pneumoniae (S.p.), are known to cause severe pneumonia. It is well known that the host response has an important role in disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation and has been previously shown to contribute to disease severity in numerous infections. Other studies in mice indicate that IL-1β levels are dramatically elevated during IAV-S.p. coinfection. However, the regulation of IL-1β during coinfection is unknown. Here, we report the NLRP3 inflammasome is the major inflammasome regulating IL-1β activation during coinfection. Furthermore, elevated IL-1β mRNA expression is due to enhanced TLR2-MYD88 signaling, which increases the amount of pro-IL-1β substrate for the inflammasome to process. Finally, NLRP3 and high IL-1β levels were associated with increased bacterial load in the brain. Our results show the NLRP3 inflammasome is not protective during IAV-S.p. coinfection.
PMID: 30794604 DOI: 10.1371/journal.pone.0212236
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[h=1]Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae.[/h] Rodriguez AE[SUP]1[/SUP], Bogart C[SUP]1[/SUP], Gilbert CM[SUP]2[/SUP], McCullers JA[SUP]3[/SUP], Smith AM[SUP]3[/SUP], Kanneganti TD[SUP]4[/SUP], Lupfer CR[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Viral-bacterial coinfections, such as with influenza A virus and Streptococcus pneumoniae (S.p.), are known to cause severe pneumonia. It is well known that the host response has an important role in disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation and has been previously shown to contribute to disease severity in numerous infections. Other studies in mice indicate that IL-1β levels are dramatically elevated during IAV-S.p. coinfection. However, the regulation of IL-1β during coinfection is unknown. Here, we report the NLRP3 inflammasome is the major inflammasome regulating IL-1β activation during coinfection. Furthermore, elevated IL-1β mRNA expression is due to enhanced TLR2-MYD88 signaling, which increases the amount of pro-IL-1β substrate for the inflammasome to process. Finally, NLRP3 and high IL-1β levels were associated with increased bacterial load in the brain. Our results show the NLRP3 inflammasome is not protective during IAV-S.p. coinfection.
PMID: 30794604 DOI: 10.1371/journal.pone.0212236
Free full text