N-3-(oxododecanoyl)-L-homoserine lactone (3-O-C12-HSL), a small bacterial signaling molecule secreted by Pseudomonas aeruginosa (P. aeruginosa), can block dendritic cell (DC) maturation and participate in immune escape, but the underlying mechanism is unclear. We speculate that regulation of DC maturation and function by lncRNAs may be the mechanism by which 3-O-C12-HSL inhibits the immune response. We found that 3-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-DR and 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 through NRIR. IL-6 stimulates T cell proliferation and activation, and we found that high NRIR expression reduced IL6 levels. However, under NRIR knockdown, 3-O-C12-HSL did not decrease IL-6 expression, suggesting that 3-O-C12-HSL may affect T cell activation through NRIR. This study is the first to elucidate the important role of a lncRNA in the mechanism of 3-O-C12-HSL activity. It also provides new ideas regarding P. aeruginosa infection pathogenesis.