Epithelial IL-22RA1-Mediated Fucosylation Promotes Intestinal Colonization Resistance to an Opportunistic Pathogen

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    145
    Author
    Pham, TAN; Clare, S; Goulding, D; Arasteh, JM; Stares, MD; Browne, HP; Keane, JA; Page, AJ; Kumasaka, N; Kane, L; ...
    Date
    2014-10-08
    Source Title
    Cell Host and Microbe
    Publisher
    CELL PRESS
    University of Melbourne Author/s
    Dougan, Gordon
    Affiliation
    Microbiology and Immunology
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    Document Type
    Journal Article
    Citations
    Pham, T. A. N., Clare, S., Goulding, D., Arasteh, J. M., Stares, M. D., Browne, H. P., Keane, J. A., Page, A. J., Kumasaka, N., Kane, L., Mottram, L., Harcourt, K., Hale, C., Arends, M. J., Gaffney, D. J., Dougan, G. & Lawley, T. D. (2014). Epithelial IL-22RA1-Mediated Fucosylation Promotes Intestinal Colonization Resistance to an Opportunistic Pathogen. CELL HOST & MICROBE, 16 (4), pp.504-516. https://doi.org/10.1016/j.chom.2014.08.017.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/259497
    DOI
    10.1016/j.chom.2014.08.017
    Abstract
    Our intestinal microbiota harbors a diverse microbial community, often containing opportunistic bacteria with virulence potential. However, mutualistic host-microbial interactions prevent disease by opportunistic pathogens through poorly understood mechanisms. We show that the epithelial interleukin-22 receptor IL-22RA1 protects against lethal Citrobacter rodentium infection and chemical-induced colitis by promoting colonization resistance against an intestinal opportunistic bacterium, Enterococcus faecalis. Susceptibility of Il22ra1(-/-) mice to C. rodentium was associated with preferential expansion and epithelial translocation of pathogenic E. faecalis during severe microbial dysbiosis and was ameloriated with antibiotics active against E. faecalis. RNA sequencing analyses of primary colonic organoids showed that IL-22RA1 signaling promotes intestinal fucosylation via induction of the fucosyltransferase Fut2. Additionally, administration of fucosylated oligosaccharides to C. rodentium-challenged Il22ra1(-/-) mice attenuated infection and promoted E. faecalis colonization resistance by restoring the diversity of anaerobic commensal symbionts. These results support a model whereby IL-22RA1 enhances host-microbiota mutualism to limit detrimental overcolonization by opportunistic pathogens.

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