<i>N</i>-3-(oxododecanoyl)-L-homoserine lactone promotes the induction of regulatory T-cells by preventing human dendritic cell maturation

Li, Youqiang; Zhou, Huayou; Zhang, Yunyan; Cha, Chen; Huang, Bin; Qu, Pinghua; Zeng, Jianming; Shunmei, E; Zhang, Xuan; Liu, Jianping

doi:10.1177/1535370214564742

Cited by 13 publications

(10 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dendritic cells (DCs) stimulated by lipopolysaccharides and in the presence of 3-oxo-C12-HSL show a decrease in their proinflammatory cytokine such as IL-12 and interferon-γ (IFNγ) ( 51 – 53 ). However, reports on anti-inflammatory IL-10 are contradictory.…”

Section: Introductionmentioning

confidence: 99%

“…In both studies, the cells were stimulated by lipopolysaccharides and exposed to the same dose of 3-oxo-C12-HSL; one team reported an increase in IL-10 secretion by human DCs ( 53 ), while another group did not see any change in IL-10 production by mouse DCs ( 52 ). By modulating DCs activation through its QS molecules, P. aeruginosa suppress the adaptive immune response, favoring the establishment of chronic infection ( 52 , 53 ). 3-oxo-C12-HSL has also proapoptotic effects on humans DCs, as is the case for several cell types ( 54 ).…”

Section: Introductionmentioning

confidence: 99%

“…This results in shifting immune responses away from host-protective Th1 responses to pathogen-protective Th2 responses ( 62 ). More precisely, 3-oxo-C12-HSL is able to promote the induction of regulatory T cells such as CD4+CD25+Foxp3+ induced regulatory T cells and to enhance their IL-10 and transforming growth factor-β (TGFβ) production associated with reduced IFNγ and IL-12p70 production ( 53 ). At the molecular level, 3-oxo-C12-HSL prevents human DCs maturation by blocking the upregulation of surface molecules, including CD11c, HLA-DR, CD40, and CD80, and DCs switched to an interleukin IL-10 (high), IL-12p70 (low) phenotype ( 53 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Impact of N-Acyl-Homoserine Lactones, Quorum Sensing Molecules, on Gut Immunity

2020

View full text Add to dashboard Cite

Among numerous molecules found in the gut ecosystem, quorum sensing (QS) molecules represent an overlooked part that warrants highlighting. QS relies on the release of small molecules (auto-inducers) by bacteria that accumulate in the environment depending on bacterial cell density. These molecules not only are sensed by the microbial community but also interact with host cells and contribute to gut homeostasis. It therefore appears entirely appropriate to highlight the role of these molecules on the immune system in dysbiosis-associated inflammatory conditions where the bacterial populations are imbalanced. Here, we intent to focus on one of the most studied QS molecule family, namely, the type I auto-inducers represented by N- acyl-homoserine lactones (AHL). First described in pathogens such as Pseudomonas aeruginosa , these molecules have also been found in commensals and have been recently described within the complex microbial communities of the mammalian intestinal tract. In this mini-review, we will expound on this emergent field of research. We will first recall evidence on AHL structure, synthesis, receptors, and functions regarding interbacterial communication. Then, we will discuss their interactions with the host and particularly with agents of the innate and adaptive gut mucosa immunity. This will reveal how this new set of molecules, driven by microbial imbalance, can interact with inflammation pathways and could be a potential target in inflammatory bowel disease (IBD). The discovery of the general impact of these compounds on the detection of the bacterial quorum and on the dynamic and immune responses of eukaryotic cells opens up a new field of pathophysiology.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Impact of N-Acyl-Homoserine Lactones, Quorum Sensing Molecules, on Gut Immunity

2020

View full text Add to dashboard Cite

show abstract

“…Consequently, humanpathogenic microorganisms, including viruses, bacteria, fungi, and parasites, have developed ways to modulate DC function during infection (35,36). In addition to contact-dependent mechanisms, microorganisms can actively release soluble mediators, such as QS molecules, to modify host immune responses (27,(37)(38)(39)(40). For example, the bacterial QS molecule homoserine lactone (HSL) modulates DC maturation (37).…”

Section: Discussionmentioning

confidence: 99%

“…In addition to contact-dependent mechanisms, microorganisms can actively release soluble mediators, such as QS molecules, to modify host immune responses (27,(37)(38)(39)(40). For example, the bacterial QS molecule homoserine lactone (HSL) modulates DC maturation (37). Mechanistically, HSL blocks expression of the costimulatory molecules CD40 and CD80 and the Ag-presenting molecule HLA-DR on DC.…”

Section: Discussionmentioning

confidence: 99%

Multiple Signaling Pathways Involved in Human Dendritic Cell Maturation Are Affected by the Fungal Quorum-Sensing Molecule Farnesol

Vivas

Leonhardt

Hünniger

et al. 2019

The Journal of Immunology

View full text Add to dashboard Cite

The quorum-sensing molecule farnesol is produced by the opportunistic human fungal pathogen Candida albicans. Aside from its primary function of blocking the transition from yeast to hyphal morphotype, it has an immunomodulatory role on human dendritic cells (DC) through the alteration of surface markers, cytokine secretion, and their ability to activate T cells. Nonetheless, the molecular mechanisms by which farnesol modulates DC differentiation and maturation remained unknown. In this study, we demonstrate through transcriptional and functional assays that farnesol influences several signaling pathways during DC differentiation and in response to TLR agonists. In particular, farnesol increases the expression of the Ag-presenting glycoprotein CD1d through the nuclear receptors PPARg and RARa, as well as p38 MAPK. However, the higher expression of CD1d did not confer these DC with an enhanced capacity to activate CD1d-restricted invariant NKT cells. In the presence of farnesol, there is reduced secretion of the Th1-inducing cytokine, IL-12, and increased release of proinflammatory cytokines, as well as the anti-inflammatory cytokine IL-10. These changes are partially independent of nuclear receptor activity but, in the case of TNF-a and IL-10, dependent on NF-kB and MAPK pathways. Interestingly, renewal of the IL-12/IL-10 milieu restores the ability of farnesol-differentiated DC to activate invariant NKT, Th1, and FOXP3 + regulatory T cells. Our results show that farnesol modulates nuclear receptors, NF-kB, and MAPK-signaling pathways, thereby impairing the capacity of DC to activate several T cells subsets and potentially conferring C. albicans, an advantage in overcoming DC-mediated immunity.

show abstract