Pseudomonas aeruginosa quorum-sensing signal molecules interfere with dendritic cell-induced T-cell proliferation

Mette E Skindersoe1, Louise H Zeuthen, Susanne Brix

  • 1Center for Biomedical Microbiology, Technical University of Denmark, Lyngby, Denmark.

Insights

Pseudomonas aeruginosa quorum-sensing molecules N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and Pseudomonas quinolone signal (PQS) reduce interleukin-12 production by dendritic cells. This impairs T-cell proliferation and adaptive immune defense against infection.

Area of Science:

  • Microbiology
  • Immunology
  • Bacterial Pathogenesis

Background:

  • Pseudomonas aeruginosa virulence factors are regulated by quorum sensing.
  • N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and Pseudomonas quinolone signal (PQS) are key quorum-sensing molecules.
  • These molecules have demonstrated immune-modulating properties.

Purpose of the Study:

  • To investigate the effects of OdDHL and PQS on cytokine production by bone marrow-derived dendritic cells (BM-DCs).
  • To determine the impact of OdDHL and PQS on T-cell responses.
  • To elucidate the dual role of these molecules in bacterial infection.

Main Methods:

  • Stimulation of BM-DCs with Escherichia coli lipopolysaccharide.
  • Treatment of BM-DCs with OdDHL and PQS.
  • Measurement of IL-12 and IL-10 cytokine production.
  • Assessment of T-cell proliferation following antigen stimulation of treated BM-DCs.

Main Results:

  • OdDHL and PQS significantly decreased IL-12 production by stimulated BM-DCs.
  • IL-10 release remained unaltered.
  • BM-DCs treated with OdDHL and PQS showed reduced capacity to induce T-cell proliferation in vitro.
  • A shift in DC maturation away from a pro-inflammatory T-helper type I response was observed.

Conclusions:

  • OdDHL and PQS act as immune modulators by suppressing IL-12 production and T-cell responses.
  • These molecules facilitate Pseudomonas aeruginosa infection by dampening adaptive immunity.
  • OdDHL and PQS exhibit dual functions: inducing virulence and modulating the host immune system.

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