AUTHOR=Gu Yinuo , Hsu Alan Chen-Yu , Zuo Xu , Guo Xiaoping , Zhou Zhengjie , Jiang Shengyu , Ouyang Zhuoer , Wang Fang 

TITLE=Chronic exposure to low-level lipopolysaccharide dampens influenza-mediated inflammatory response via A20 and PPAR network

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1119473

DOI=10.3389/fimmu.2023.1119473

ISSN=1664-3224

ABSTRACT=<p>Influenza A virus (IAV) infection leads to severe inflammation, and while epithelial-driven inflammatory responses occur <italic>via</italic> activation of NF-κB, the factors that modulate inflammation, particularly the negative regulators are less well-defined. In this study we show that A20 is a crucial molecular switch that dampens IAV-induced inflammatory responses. Chronic exposure to low-dose LPS environment can restrict this excessive inflammation. The mechanisms that this environment provides to suppress inflammation remain elusive. Here, our evidences show that chronic exposure to low-dose LPS suppressed IAV infection or LPS stimulation-induced inflammation <italic>in vitro</italic> and <italic>in vivo</italic>. Chronic low-dose LPS environment increases A20 expression, which in turn positively regulates PPAR-α and -γ, thus dampens the NF-κB signaling pathway and NLRP3 inflammasome activation. Knockout of A20 abolished the inhibitory effect on inflammation. Thus, A20 and its induced PPAR-α and -γ play a key role in suppressing excessive inflammatory responses in the chronic low-dose LPS environment.</p>