Essential role of Salmonella Enteritidis DNA adenine methylase in modulating inflammasome activation

Abstract

Background: Salmonella Enteritidis (SE) is one of the major foodborne zoonotic pathogens of worldwide importance which can induce activation of NLRC4 and NLRP3 inflammasomes during infection. Given that the inflammasomes play an essential role in resisting bacterial infection, Salmonella has evolved various strategies to regulate activation of the inflammasome, most of which largely remain unclear.Results: A transposon mutant library in SE strain C50336 was screened for the identification of the potential factors that regulate inflammasome activation. We found that T3SS-associated genes invC, prgH, and spaN were required for inflammasome activation in vitro. Interestingly, C50336 strains with deletion or overexpression of Dam were both defective in activation of caspase-1 and secretion of IL-1β. Transcriptome sequencing (RNA-seq) results suggest that the absence and overexpression of Dam had similar effects on infected cells, as high overlapping rates of differentially expressed genes and enriched pathways were found between the C50336-VS-C50336Δdam and C50336-VS-C50336::dam groups, including multiple signaling pathways related to the inflammasome. Moreover, overexpression of Dam in macrophages by lentiviral infection could specifically promote the activation of the NLRP3 inflammasome independently.Conclusions: These data indicate that Dam was essential for modulating inflammasome activation during SE infection, there are complex and dynamic interplays between Dam and the inflammasome under different conditions. New insights were provided about the battle between SE and host innate immunological mechanisms.