Regulatory role of suppressive motifs from commensal DNA

N. Bouladoux, J. A. Hall, J. R. Grainger, L. M. Dos Santos, M. G. Kann, V. Nagarajan, D. Verthelyi, Y. Belkaid

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The microbiota contributes to the induction of both effector and regulatory responses in the gastrointestinal (GI) tract. However, the mechanisms controlling these distinct properties remain poorly understood. We previously showed that commensal DNA promotes intestinal immunity. Here, we find that the capacity of bacterial DNA to stimulate immune responses is species specific and correlated with the frequency of motifs known to exert immunosuppressive function. In particular, we show that the DNA of Lactobacillus species, including various probiotics, is enriched in suppressive motifs able to inhibit lamina propria dendritic cell activation. In addition, immunosuppressive oligonucleotides sustain T reg cell conversion during inflammation and limit pathogen-induced immunopathology and colitis. Altogether, our findings identify DNA-suppressive motifs as a molecular ligand expressed by commensals and support the idea that a balance between stimulatory and regulatory DNA motifs contributes to the induction of controlled immune responses in the GI tract and gut immune homeostasis. Further, our findings suggest that the endogenous regulatory capacity of DNA motifs enriched in some commensal bacteria could be exploited for therapeutic purposes. © 2012 Society for Mucosal Immunology.
    Original languageEnglish
    Pages (from-to)623-634
    Number of pages11
    JournalMucosal Immunology
    Volume5
    Issue number6
    DOIs
    Publication statusPublished - Nov 2012

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