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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.
Abstract:
Pseudomonas aeruginosa releases a wide array of toxins and tissue-degrading enzymes. Production of these malicious virulence factors is controlled by interbacterial communication in a process known as quorum sensing. An increasing body of evidence reveals that the bacterial signal molecule N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) exhibits both quorum-sensing signalling and immune-modulating properties. Recently, yet another quorum-sensing signal molecule, the Pseudomonas quinolone signal (PQS), has been shown to affect cytokine release by mitogen-stimulated human T cells. In the present article we demonstrate that both OdDHL and PQS decrease the production of interleukin-12 (IL-12) by Escherichia coli lipopolysaccharide-stimulated bone marrow-derived dendritic cells (BM-DCs) without altering their IL-10 release. Moreover, BM-DCs exposed to PQS and OdDHL during antigen stimulation exhibit a decreased ability to induce T-cell proliferation in vitro. Collectively, this suggests that OdDHL and PQS change the maturation pattern of stimulated DCs away from a proinflammatory T-helper type I directing response, thereby decreasing the antibacterial activity of the adaptive immune defence. OdDHL and PQS thus seem to possess dual activities in the infection process: as inducers of virulence factors as well as immune-modulators facilitating the infective properties of this pathogen.
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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