Pathogenic bacteria use quorum-sensing signal molecules to co-ordinate the expression of virulence genes. Animal-based studies have demonstrated the immunomodulatory effects of quorum-sensing signal molecules. In the present study, we have examined the impact of these molecules on normal human immune function in vitro and compared this with immune changes in patients with sepsis where quorum-sensing signal molecules were detected in the sera of patients. Quorum-sensing signal molecules inhibited normal dendritic cell and T-cell activation and proliferation, and down-regulated the expression of co-stimulatory molecules on dendritic cells; in MLDCRs (mixed lymphocyte dendritic cell reactions), secretion of IL (interleukin)-4 and IL-10 was enhanced, but TNF-α (tumour necrosis factor-α), IFN-γ (interferon-γ) and IL-6 was reduced. Quorum-sensing signal molecules induced apoptosis in dendritic cells and CD4+ cells, but not CD8+ cells. Dendritic cells from patients with sepsis were depleted and ex vivo showed defective expression of co-stimulatory molecules and dysfunctional stimulation of allogeneic T-lymphocytes. Enhanced apoptosis of dendritic cells and differential CD4+ Th1/Th2 (T-helper 1/2) cell apoptotic rate, and modified Th1/Th2 cell cytokine profiles in MLDCRs were also demonstrated in patients with sepsis. The pattern of immunological changes in patients with sepsis mirrors the effects of quorum-sensing signal molecules on responses of immune cells from normal individuals in vitro, suggesting that quorum-sensing signal molecules should be investigated further as a cause of immune dysfunction in sepsis.
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December 2008
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Research Article|
November 03 2008
Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis
Pisake Boontham;
Pisake Boontham
*Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
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Adrian Robins;
Adrian Robins
†Division of Immunology, University of Nottingham, Nottingham NG7 2UH, U.K.
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Palanichamy Chandran;
Palanichamy Chandran
*Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
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David Pritchard;
David Pritchard
‡School of Pharmacy, University of Nottingham, Nottingham NG7 2UH, U.K.
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Miguel Cámara;
Miguel Cámara
§Institute of Infection, Immunity and Inflammation, University of Nottingham, Nottingham NG7 2UH, U.K.
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Paul Williams;
Paul Williams
§Institute of Infection, Immunity and Inflammation, University of Nottingham, Nottingham NG7 2UH, U.K.
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Suebwong Chuthapisith;
Suebwong Chuthapisith
*Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
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Alasdair McKechnie;
Alasdair McKechnie
*Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
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Brian J. Rowlands;
Brian J. Rowlands
*Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
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Oleg Eremin
*Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.
Correspondence: Professor Oleg Eremin (email [email protected]).
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Publisher: Portland Press Ltd
Received:
January 17 2008
Revision Received:
March 06 2008
Accepted:
March 25 2008
Accepted Manuscript online:
March 25 2008
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2008 Biochemical Society
2008
Clin Sci (Lond) (2008) 115 (11): 343–351.
Article history
Received:
January 17 2008
Revision Received:
March 06 2008
Accepted:
March 25 2008
Accepted Manuscript online:
March 25 2008
Citation
Pisake Boontham, Adrian Robins, Palanichamy Chandran, David Pritchard, Miguel Cámara, Paul Williams, Suebwong Chuthapisith, Alasdair McKechnie, Brian J. Rowlands, Oleg Eremin; Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in human sepsis. Clin Sci (Lond) 1 December 2008; 115 (11): 343–351. doi: https://doi.org/10.1042/CS20080018
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