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- Title
N-3-(oxododecanoyl)-L-homoserine lactone promotes the induction of regulatory T-cells by preventing human dendritic cell maturation.
- Authors
Youqiang Li; Huayou Zhou; Yunyan Zhang; Cha Chen; Bin Huang; Pinghua Qu; Jianming Zeng; Shunmei E.; Xuan Zhang; Jianping Liu
- Abstract
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 lipo-polysaccharide (LPS)-induced maturation. At the molecular level, C12 blocked the upregulation of surface molecules, including CD11c, HLA-DR, CD40, and CD80, and it switched to an interleukin (IL)-10high, IL-12p70low phenotype. Moreover, C12 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 transforming growth factor (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.
- Publication
Experimental Biology & Medicine, 2015, Vol 240, Issue 7, p896
- ISSN
1535-3702
- Publication type
Article
- DOI
10.1177/1535370214564742