Year: 2013
Type: dissertation
Abstract: \nThe mammalian gastrointestinal tract is home to a complex microbial community \nengaged in a dynamic interaction with the immune system. Mucus is the first point of \ncontact of the microbiota with the host, acting as a first line of defence. Furthermore γδ \nintraepithelial lymphocytes (IELs) respond to the invading bacteria that circumvent the \nmucus barrier. In this study two approaches were used to investigate the role of mucus \nin intestinal homeostasis; firstly the impact of γδ IELs on the mucus layer, and secondly \nthe adhesion properties of the gut symbiont Lactobacillus reuteri to mucus. \nTo study the impact of IELs on mucus properties, a γδ T cell-deficient (TCRδ-/-) mouse \nmodel was used. TCRδ-/- mice showed increased susceptibility to dextran sodium \nsulphate (DSS)-induced colitis, alterations in mucin expression, glycosylation and \ngoblet cell numbers, but maintained an intact mucus layer in vivo. Moreover, TCRδ-/- \nmice showed reduced levels of interleukin-33 mRNA, a mediator of mucosal healing. \nAn ex vivo SI organoid model using input cells from TCRδ-/- mice showed, upon \naddition of keratinocyte growth factor, increases in crypt length, and both goblet cell \nnumbers and redistribution. These findings provide novel mechanisms by which γδ \nIELs may modulate mucus properties, explaining the increased susceptibility of TCRδ-/- \nmice to chemically-induced colitis. \nL. reuteri strains protect against DSS-induced colitis in mice. To investigate the \nimportance of L. reuteri adhesion to the intestinal mucus layer, the mucus-producing \nHT29-MTX cell line as well as murine and human intestinal tissues were used in \nconjunction with chemical treatments. The mucus-binding protein MUB of L. reuteri \nATCC 53608 was found to promote L. reuteri adhesion to mucins in a host and tissuespecific \nmanner and display sialic acid-binding specificities. Together, these data \nprovide insights into L. reuteri-mucus interactions; a key factor in influencing host \nresponse and exerting health effects.
Author: Olivia Kober
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W770377307