Gossip in the gut: Quorum sensing, a new player in the host-microbiota interactions

Table 1 Examples of bacterial quorum sensing autoinducer and corresponding systems

	AI	Example of producing bacteria	QS system	Bacterial QS-regulated processes	Ref.
Gram +	AI peptide	Staphylococcus aureus	agr	Virulence	Novick et al[155]
		Listeria monocytogenes	agr	Virulence	Autret et al[156]
		Clostridium perfringens	agr	Virulence	Ohtani et al[157]
		Enterococcus faecalis	FsR	Virulence	Sifri et al[158]
		Bacillus subtilis	com	Competence	Magnuson et al[159]
	γ-butyrolactone	Streptomyces genus	scb	Antibiotics	Takano et al[13]
			scg	Metabolism	Du et al[14]
Gram -	AI-1 (acyl-homoserine lactones)	Vibrio fischeri	LuxI/LuxR	Luminescence	Engebrecht et al[16]
		Vibrio harveyi	LuxLM/LuxN	Luminescence	Mok et al[160]
				Virulence	Waters and Bassler[161]
		Pseudomonas aeruginosa	LasI/LasR	Virulence and biofilm	Gambello and Iglewski[162], Gambello et al[163], Winson et al[164], and Chapon-Hervé et al[165]
			RhlI/RhlR
	PQS	Pseudomonas aeruginosa	PqsABCD/PqsR	QS regulation	Pesci et al[166]
				Pyocyanin	Gallagher et al[167]
				Iron homeostasis	Bredenbruch et al[168] and Diggle et al[169]
				Virulence	Gallagher et al[167] and Cao et al[170]
				Biofilm	Diggle et al[171]
	IQS	Pseudomonas aeruginosa	AmbBCDE/IqsR	Response to stress	Lee et al[172]
	CAI	Vibrio (cholerae)	CqsA/CqsS	Virulence	Ng et al[173]
	AI-3	EHEC O157:H7	Qse/QseBC	Attachment-effacement	Sperandio et al[19], Walters et al[21], and Kim et al[22]
		EPEC O26:H11	Qse/unknown	Unknown	Kim et al[22], and Kaper and Sperandio[40]
		AIEC LF82	Qse/unknown	Unknown	Kim et al[22]
		Escherichia coli MG1655	Unknown	Unknown	Kim et al[22]
		Escherichia coli BW25113	Unknown	Unknown	Kim et al[22]
		Salmonella enterica	Qse/unknown	Unknown	Kim et al[22], Kaper and Sperandio[40], and Walters and Sperandio[174]
		Shigella flexneri	Qse/unknown	Unknown	Kim et al[22], Kaper and Sperandio[40], and Walters and Sperandio[174]
		Yersinia sp.	Qse/unknown	Unknown	Kim et al[22], Kaper and Sperandio[40], and Walters and Sperandio[174]
Gram + and -	AI-2	Vibrio harveyi	LuxS/LuxPQ	Bioluminescence, TSS, protease	Surette et al[24], Mok et al[160], and Schauder et al[175]
		Vibrio cholerae	LuxS/LuxPQ	Virulence and Biofilm	Schauder et al[175], Zhu et al[176], and Hammer and Bassler[177]
		Enterococcus faecalis	LuxS/LuxPQ	Unknown	Surette et al[24], and Schauder et al[175]
		EHEC	LuxS/LsrB (?)	Attachment-effacement	Schauder et al[175], and Bansal et al[178]
		Salmonella enterica	LuxS/LsrB	Pathogenicity and invasion	Miller et al[26], Schauder et al[175], and Choi et al[179]

AI: Autoinducer; AIEC: Adherent-invasive Escherichia coli; AIP: AutoInducer peptides; CAI: Cholera autoinducer-1; EHEC: Enterohemorrhagic Escherichia coli; EPEC: Enteropathogenic Escherichia coli; IQS: Integrated quorum sensing; PQS: Pseudomonas quinolone signal; QS: Quorum sensing.

Table 2 Effects of quorum sensing molecules on different parameters of the intestinal epithelial barrier function

QS molecule	Effects	Ref.
Effects on the intestinal epithelial migration
3-oxo-C12-HSL	Increased migration at low concentrations (1.5-12 μmol/L) vs inhibition at 200 μmol/L	Karlsson et al[72]
	Interaction with IQGAP1 and increase in Rac1/Cdc42 (1.5-200 μmol/L)	Karlsson et al[72]
Effects on the intestinal epithelial permeability and intercellular junctions
3-oxo-C12-HSL	Increased permeability to ions and macromolecules (100-400 μmol/L)	Eum et al[55], Vikström et al[58-60], and Aguanno et al[61]
	Activation of p38 and p42/44 and calcium signaling (100-200 μmol/L)	Vikström et al[58-60]
	Decreased expression levels of tight junction genes (100-400 μmol/L); Disassembly of tight and adherens junctions (modification of their phosphorylation status and involvement of MMP-2 and -3)	Eum et al[55], Vikström et al[58-60], and Aguanno et al[61]
	Decreased levels of tight junction proteins occludin and tricellulin (100-400 μmol/L)	Eum et al[55]
	Decreased protein levels of extracellular matrix and tight junction proteins (400 μmol/L)	Tao et al[62]
3-oxo-C12:2-HSL	No deleterious effects on permeabilityProtection of tight junction integrity and maintenance of junctional complexes at the plasma membrane under pro-inflammatory conditions	Landman et al[39] and Aguanno et al[61]
3-oxo-C14-HSL	Decreased protein levels of extracellular matrix and tight junction proteins (400 μmol/L)	Tao et al[62]
Indole and indole derivatives	Decreased permeability to ions and increased expression of genes coding tight junction and cytoskeleton proteins	Bansal et al[76] and Shimada et al[77]
	Decreased permeability to macromolecules	Venkatesh et al[79]
	Increased transcripts levels of genes coding tight junction proteins	Shin et al[78]
Effects on the mucus layer components
3-oxo-C12-HSL	Decreased MUC3 mRNA levels (30 μmol/L)	Taguchi et al[70]
	Decrease in Muc2 production in goblet cell-like cell line (100 μmol/L) vs increase in colonic cell line (400 μmol/L)	Tao et al[67]
Indole	Increased expression of genes involved in the production of mucins	Bansal et al[76]
Effects on intestinal epithelial cell viability
3-oxo-C12-HSL	Mitochondrial dysfunction and induction of apoptosis in goblet cell-like cell line (100 μmol/L) and in colonic cell line (30-100 μmol/L)	Tao et al[67-69], and Taguchi et al[70]
	Induction of apoptosis, mitochondrial dysfunction, oxidative stress and blocking of cell cycle (400 μmol/L)	Tao et al[62]
3-oxo-C14-HSL	Induction of apoptosis, mitochondrial dysfunction, oxidative stress and blocking of cell cycle (400 μmol/L)	Eum et al[55], Vikström et al[58-60], Aguanno et al[61], and Tao et al[62]
CSF	Reduction of oxidative stress-induced cell death and loss of the epithelial barrier (involving HSP27 and p38/MAPK pathway)	Fujiya et al[74]

CSF: Competence and sporulation factor; HSL: Homoserine lactones; HSP27: Heat shock protein 27; IQGAP1: IQ motif containing GTPase activating protein 1; MAPK: Mitogen-activated protein kinase; MMP-2/-3: Matrix metalloproteinase-2/-3; MUC: Mucin; QS: Quorum sensing; Rac1/Cdc42: Ras-related C3 botulinum toxin substrate 1/cell division control protein 42 homolog.

Table 3 Effects of quorum sensing molecules on inflammation in different cell types

Cell type	QS molecule	Effects	Ref.
Effects on innate immune cells
Macrophages	3-oxo-C12-HSL	Anti-inflammatory effects on IL-12 and TNF-α (0.1-100 μmol/L)	Telford et al[94]
		Increased TLR2 and TLR4 expression and decreased TNF-α production (1-100 μmol/L)	Bao et al[180]
		Pro-apoptotic effects (12-50 μmol/L)	Tateda et al[102]
		Increased phagocytosis (100 μmol/L)	Vikström et al[107]
		NF-κB inhibition (4.7 μmol/L)	Kravchenko et al[104]
		Dose-dependent anti-inflammatory effects (1-50 μmol/L)	Kravchenko et al[105]
		Involvement in p38/MAPK signaling (1-100 μmol/L)	Kravchenko et al[105], Vikström et al[107], Glucksam-Galnoy et al[181]
		Activation of the Unfolded Protein Response (6.25-100 μmol/L)	Zhang et al[182]
		Change in cell volume and shape (10-50 μmol/L)	Holm et al[183]
	Indole derivatives	Prevents the induction of pro-inflammatory cytokines	Krishnan et al[184]
	AI-2	Induction of the expression of cytokines, chemokines and TNFSF9	Li et al[41]
Monocytes	AI-3 and analogues	Increase in IL-8 secretion	Kim et al[22]
Dendritic cells	3-oxo-C12-HSL	Pro-apoptotic effects (100 μmol/L)	Boontham et al[185]
		No effect on IL-10 secretion (5-30 μmol/L)	Skindersoe et al[100]
		Increased IL-10 production (5-100 μmol/L)	Li et al[99]
		Decreased IL-12 secretion (5-100 μmol/L)	Li et al[99] and Skindersoe et al[100]
		Increased induction of Treg (5-100 μmol/L)	Li et al[99]
Neutrophils	3-oxo-C12-HSL	Chemoattraction (0.01-100 μmol/L)	Karlsson et al[186] and Zimmermann et al[187]
		Activation of MAPK signaling (12-50 μmol/L)	Tateda et al[102] and Singh et al[188]
		Increased phagocytosis (10 μmol/L)	Wagner et al[189]
		Pro-apoptotic effects (12-50 μmol/L)	Tateda et al[102]
Effects on adaptive immune cells
T cells	3-oxo-C12-HSL	Inhibition of proliferation and activation (0.1-100 μmol/L)	Telford et al[94], Boontham et al[185], Gupta et al[190], and Hooi et al[191]
		Activation of naïve T cells towards Th1 phenotype (5 μmol/L)	Smith et al[95]
		Decreased secretion of IL-4 and IFN-γ (5 μmol/L)	Ritchie et al[96]
		Induction of apoptosis via the mitochondria pathway (100 μmol/L)	Jacobi et al[101]
		Induction of Treg (1-50 μmol/L)	Li et al[99]
	Indole derivatives	Re-programming into tolerogenic T cells	Cervantes-Barragan et al[192]
		Promotion of differentiation towards a regulatory type 1 phenotype	Aoki et al[193]
B cells	3-oxo-C12-HSL	Modulation of immunoglobulin production (0.1-100 μmol/L)	Telford et al[94] and Ritchie et al[194]
ILC	Indole derivatives	Promotion of IL-22 production	Zelante et al[83]
Effects on epithelial cells
Pulmonary tract epithelial cells	3-oxo-C12-HSL	Induction of IL-8 production and NF-B activation (100 μmol/L)	Smith et al[195]
		Increased expression levels of pro-inflammatory cytokines	Jahoor et al[115]
Intestinal epithelial cells	3-oxo-C12-HSL	Mitigation (1-10 μmol/L) or aggravation (> 50 μmol/L) of IL-8 expression induction	Peyrottes et al[92]
	3-oxo-C12:2-HSL	Attenuation of the induction of IL-8 expression (5-50 μmol/L)	Landman et al[39]

AI: Autoinducer; B cells: Lymphocytes B; HSL: Homoserine lactones; IFN-γ: Interferon-γ; IL: Interleukin; ILC: Innate lymphoid cells; MAPK: Mitogen-activated protein kinase; NF-κB: Nuclear factor-kappa B; QS: Quorum sensing; T cells: Lymphocytes T; Th: T helper; TLR: Toll like receptors; TNF-α: Tumor necrosis factor-α; Treg: Regulatory T cells.