N-3-(oxododecanoyl)-L-homoserine lactone (C12) is a small bacterial signaling molecule secreted by Pseudomonas aeruginosa (PA), which activates mammalian cells through TLR4-independent mechanisms.C12 acts as an immunosuppressant and it has been shown to modulate murine bone marrow-derived dendritic cell-mediated T-helper 2 (Th2) cell polarizations in vitro.In the present study, we initially examined the impact of C12 on the maturation of human monocyte-derived dendritic cells (Mo-DCs) and the induction of regulatory T-cells (iTregs) in culture.Our findings demonstrate that C12-treated Mo-DCs failed to undergo lipopolysaccharide (LPS)-induced maturation.At the molecular level, C12 blocked the upregulation of surface molecules, including CD1 lc, MHC Ⅱ, CD40, and CD80, and it switched to an interleukin (IL)-10high, IL-12p70low phenotype.Moreover, C 12 selectively inhibited the capacity of Mo-DCs to stimulate the proliferation of allogeneic CD4+ T-cells.Otherwise, the C12-treated Mo-DCs promoted the generation of CD4+CD25+Foxp3+-induced regulatory T-cells (iTregs)and enhanced their IL-10 and TGF-β production associated with reduced interferon (IFN)-γ and IL-12p70 production.These findings provide new insights towards understanding the persistence of chronic inflammation in PA infection.