Open AccessEnhanced IL-1β production is mediated by a TLR2-MYD88-NLRP3 signaling axis during coinfection with influenza A virus and Streptococcus pneumoniae
Author(s) -
Angeline E. Rodriguez,
Christopher Bogart,
Christopher Gilbert,
Jonathan A. McCullers,
Amber M. Smith,
ThirumalaDevi Kanneganti,
Christopher R. Lupfer
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0212236
Subject(s) - coinfection , inflammasome , tlr2 , streptococcus pneumoniae , influenza a virus , immunology , microbiology and biotechnology , immune system , biology , cytokine , virus , inflammation , innate immune system , antibiotics
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.