N-3-(oxododecanoyl)-L-homoserine lactone promotes the induction of regulatory T-cells by preventing human dendritic cell maturation.
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 CD11c, HLA-DR, CD40, and CD80, and it switched to an interleukin (IL)-10(high), IL-12p70(low) 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.
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China Guangzhou University of Chinese Medicine, Guangzhou 510006, P.R. China.
Youqiang
Y
Li
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China.
Huayou
H
Zhou
Department of Stomatology, Guangzhou Women and Children's Medical Center, Guangzhou 510623, P.R. China.
Yunyan
Y
Zhang
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China chencha906@163.com.
Cha
C
Chen
Department of Laboratory Medicine, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, P.R. China.
Bin
B
Huang
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China.
Pinghua
P
Qu
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China.
Jianming
J
Zeng
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China.
E
E
Shunmei
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China.
Xuan
X
Zhang
Department of Laboratory Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou 510006, P.R. China.
Jianping
J
Liu
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000187:drug effects*; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*
C088386:homoserine lactone; D015107:4-Butyrolactone
Pseudomonas aeruginosa; dendritic cells; regulatory T-cells