The role of mucus in the cross talk between gut bacteria and the host

Kober, Olivia (2013) The role of mucus in the cross talk between gut bacteria and the host. Doctoral thesis, University of East Anglia.

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    The mammalian gastrointestinal tract is home to a complex microbial community
    engaged in a dynamic interaction with the immune system. Mucus is the first point of
    contact of the microbiota with the host, acting as a first line of defence. Furthermore γδ
    intraepithelial lymphocytes (IELs) respond to the invading bacteria that circumvent the
    mucus barrier. In this study two approaches were used to investigate the role of mucus
    in intestinal homeostasis; firstly the impact of γδ IELs on the mucus layer, and secondly
    the adhesion properties of the gut symbiont Lactobacillus reuteri to mucus.
    To study the impact of IELs on mucus properties, a γδ T cell-deficient (TCRδ-/-) mouse
    model was used. TCRδ-/- mice showed increased susceptibility to dextran sodium
    sulphate (DSS)-induced colitis, alterations in mucin expression, glycosylation and
    goblet cell numbers, but maintained an intact mucus layer in vivo. Moreover, TCRδ-/-
    mice showed reduced levels of interleukin-33 mRNA, a mediator of mucosal healing.
    An ex vivo SI organoid model using input cells from TCRδ-/- mice showed, upon
    addition of keratinocyte growth factor, increases in crypt length, and both goblet cell
    numbers and redistribution. These findings provide novel mechanisms by which γδ
    IELs may modulate mucus properties, explaining the increased susceptibility of TCRδ-/-
    mice to chemically-induced colitis.
    L. reuteri strains protect against DSS-induced colitis in mice. To investigate the
    importance of L. reuteri adhesion to the intestinal mucus layer, the mucus-producing
    HT29-MTX cell line as well as murine and human intestinal tissues were used in
    conjunction with chemical treatments. The mucus-binding protein MUB of L. reuteri
    ATCC 53608 was found to promote L. reuteri adhesion to mucins in a host and tissuespecific
    manner and display sialic acid-binding specificities. Together, these data
    provide insights into L. reuteri-mucus interactions; a key factor in influencing host
    response and exerting health effects.

    Item Type: Thesis (Doctoral)
    Faculty \ School: Faculty of Science > School of Biological Sciences
    Depositing User: Mia Reeves
    Date Deposited: 06 Mar 2014 12:54
    Last Modified: 06 Mar 2014 12:54

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