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

Mette Elena Skindersø, Louise Zeuthen, Susanne Brix Pedersen, Lisbeth Nielsen Fink, James Lazenby, Christine Whittall, Paul Williams, Stephen P. Diggle, Hanne Frøkiær, Margaret Cooley, Michael Christian Givskov

    Research output: Contribution to journalJournal articleResearchpeer-review

    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.
    Original languageEnglish
    JournalF E M S Immunology and Medical Microbiology
    Volume55
    Issue number3
    Pages (from-to)335-345
    ISSN0928-8244
    DOIs
    Publication statusPublished - 2009

    Keywords

    • dendritic cell
    • quorum sensing
    • immunomodulation
    • PQS
    • Pseudomonas aeruginosa
    • OdDHL

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