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

Abstract 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.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2013

Author dc:creator

• Kober, Olivia

Language dc:language

en