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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

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 inflammati...

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Autores principales: Rodriguez, Angeline E., Bogart, Christopher, Gilbert, Christopher M., McCullers, Jonathan A., Smith, Amber M., Kanneganti, Thirumala-Devi, Lupfer, Christopher R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386446/
https://www.ncbi.nlm.nih.gov/pubmed/30794604
http://dx.doi.org/10.1371/journal.pone.0212236
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author Rodriguez, Angeline E.
Bogart, Christopher
Gilbert, Christopher M.
McCullers, Jonathan A.
Smith, Amber M.
Kanneganti, Thirumala-Devi
Lupfer, Christopher R.
author_facet Rodriguez, Angeline E.
Bogart, Christopher
Gilbert, Christopher M.
McCullers, Jonathan A.
Smith, Amber M.
Kanneganti, Thirumala-Devi
Lupfer, Christopher R.
author_sort Rodriguez, Angeline E.
collection PubMed
description 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.
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spelling pubmed-63864462019-03-09 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 A. Smith, Amber M. Kanneganti, Thirumala-Devi Lupfer, Christopher R. PLoS One Research Article 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. Public Library of Science 2019-02-22 /pmc/articles/PMC6386446/ /pubmed/30794604 http://dx.doi.org/10.1371/journal.pone.0212236 Text en © 2019 Rodriguez et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rodriguez, Angeline E.
Bogart, Christopher
Gilbert, Christopher M.
McCullers, Jonathan A.
Smith, Amber M.
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
title Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae
title_full Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae
title_fullStr Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae
title_full_unstemmed Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae
title_short Enhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae
title_sort enhanced il-1β production is mediated by a tlr2-myd88-nlrp3 signaling axis during coinfection with influenza a virus and streptococcus pneumoniae
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386446/
https://www.ncbi.nlm.nih.gov/pubmed/30794604
http://dx.doi.org/10.1371/journal.pone.0212236
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