Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae

Angeline E. Rodriguez, Christopher Bogart, Christopher M. Gilbert, Jonathan Mccullers, Amber Smith, Thirumala Devi Kanneganti, Christopher R. Lupfer

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0212236
JournalPloS one
Volume14
Issue number2
DOIs
StatePublished - Feb 1 2019

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Streptococcus pneumoniae
Influenza A virus
interleukin-1
Coinfection
mixed infection
Interleukin-1
Viruses
Inflammasomes
Bacterial Load
disease severity
pneumonia
Brain
Pneumonia
cytokines
inflammation
Chemical activation
Cytokines
Inflammation
brain
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae. / Rodriguez, Angeline E.; Bogart, Christopher; Gilbert, Christopher M.; Mccullers, Jonathan; Smith, Amber; Kanneganti, Thirumala Devi; Lupfer, Christopher R.

In: PloS one, Vol. 14, No. 2, e0212236, 01.02.2019.

Research output: Contribution to journalArticle

Rodriguez, Angeline E. ; Bogart, Christopher ; Gilbert, Christopher M. ; Mccullers, Jonathan ; Smith, Amber ; Kanneganti, Thirumala Devi ; Lupfer, Christopher R. / Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae. In: PloS one. 2019 ; Vol. 14, No. 2.
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