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Significant immunomodulatory effects of Pseudomonas aeruginosa quorum-sensing signal molecules: possible link in

Pisake Boontham1, Adrian Robins, Palanichamy Chandran

  • 1Division of Surgery, University of Nottingham, Nottingham NG7 2UH, U.K.

Clinical Science (London, England : 1979)
|March 28, 2008
PubMed

Insights

Quorum-sensing signal molecules impair human immune cells, inhibiting dendritic cell and T-cell responses. These molecules may cause immune dysfunction in sepsis patients, mirroring in vitro findings.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Pathogenic bacteria utilize quorum-sensing signal molecules to regulate virulence gene expression.
  • Animal studies suggest quorum-sensing signal molecules possess immunomodulatory properties.

Purpose of the Study:

  • To investigate the impact of quorum-sensing signal molecules on normal human immune function in vitro.
  • To compare these effects with immune changes observed in sepsis patients with detectable quorum-sensing signal molecules in their sera.

Main Methods:

  • Assessed the effects of quorum-sensing signal molecules on dendritic cell and T-cell activation, proliferation, and apoptosis in vitro.
  • Analyzed cytokine profiles (IL-4, IL-10, TNF-alpha, IFN-gamma, IL-6) in mixed lymphocyte dendritic cell reactions (MLDCRs).
  • Examined immune cell function, including dendritic cell apoptosis and T-helper cell profiles, in sepsis patients.

Main Results:

  • Quorum-sensing signal molecules inhibited dendritic cell and T-cell activation and proliferation, down-regulated co-stimulatory molecules, and induced apoptosis in dendritic cells and CD4(+) T-cells.
  • In MLDCRs, these molecules enhanced IL-4 and IL-10 secretion while reducing TNF-alpha, IFN-gamma, and IL-6.
  • Sepsis patients exhibited depleted dendritic cells with defective co-stimulatory molecule expression and impaired T-lymphocyte stimulation, mirroring in vitro findings.

Conclusions:

  • Quorum-sensing signal molecules adversely affect normal human immune cell function in vitro.
  • The observed immunological alterations in sepsis patients align with the effects of quorum-sensing signal molecules.
  • Quorum-sensing signal molecules warrant further investigation as a potential cause of immune dysfunction in sepsis.

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