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

PloS One
Angeline E RodriguezChristopher R Lupfer

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.

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Citations

Sep 11, 2019·Cold Spring Harbor Perspectives in Biology·Carolyn A Lacey, Edward A Miao
Aug 8, 2020·Immunological Reviews·Meagan D Rippee-BrooksChristopher R Lupfer
Feb 9, 2021·BioMed Research International·Huihui ZhangYuanyi Peng
Apr 9, 2021·Frontiers in Cellular and Infection Microbiology·Vicky SenderBirgitta Henriques-Normark
Jun 3, 2021·International Journal of Molecular Sciences·Janine J WildenYvonne Boergeling
Nov 18, 2021·Clinical Microbiology Reviews·Fabián SalazarAdilia Warris
Dec 18, 2021·Frontiers in Medicine·Sofija Sekulic MarkovicIvan Jovanovic

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Methods Mentioned

BETA
ELISA
PCR
flow cytometry

Software Mentioned

PRISM
PRISM6
Graphpad

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