N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL), a small bacterial signaling molecule secreted byPseudomonas aeruginosa (P. aeruginosa), can block dendritic cell (DC) maturation and participate in immuneescape, but the underlying mechanism is unclear. We speculate that regulation of DC maturation and functionby lncRNAs may be the mechanism by which 3-O-C12-HSL inhibits the immune response. We found that3-O-C12-HSL increased the expression level of the lncRNA NRIR, impeding monocyte-derived dendritic cell(Mo-DC) maturation. In addition, we observed the effect of NRIR on the expression of CD40, CD80, HLA-DRand IL-6. NRIR overexpression significantly reduced the expression of Mo-DC surface markers, while 3-OC12-HSL did not significantly reduce the expression of Mo-DC surface markers after NRIR knockdown.These results indicate that 3-O-C12-HSL indeed affects the differentiation and maturation of Mo-DCs throughNRIR. IL-6 stimulates T cell proliferation and activation, and we found that high NRIR expression reduced IL-6 levels. However, under NRIR knockdown, 3-O-C12-HSL did not decrease IL-6 expression, suggesting that3-O-C12-HSL may affect T cell activation through NRIR. This study is the first to elucidate the important roleof a lncRNA in the mechanism of 3-O-C12-HSL activity. It also provides new ideas regarding P. aeruginosainfection pathogenesis.