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: Users 2259 not found.
Date Deposited: 06 Mar 2014 12:54
Last Modified: 06 Mar 2014 12:54

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