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

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-1? (IL-1?) 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-1? levels are dramatically elevated during IAV-S.p. coinfection. However, the regulation of IL-1? during coinfection is unknown. Here, we report the NLRP3 inflammasome is the major inflammasome regulating IL-1? activation during coinfection. Furthermore, elevated IL-1? mRNA expression is due to enhanced TLR2-MYD88 signaling, which increases the amount of pro-IL-1? substrate for the inflammasome to process. Finally, NLRP3 and high IL-1? levels were associated with increased bacterial load in the brain. Our results show the NLRP3 inflammasome is not protective during IAV-S.p. coinfection.

SUBMITTER: Rodriguez AE 

PROVIDER: S-EPMC6386446 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature