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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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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. |
format | Online Article Text |
id | pubmed-6386446 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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