Cargando…

A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS

BACKGROUND: Disruption of intestinal barrier function is important in the pathogenesis of numerous intestinal diseases and can lead to increased intestinal permeability. During infection with the protozoan parasite Giardia duodenalis, intestinal permeability is increased in part due to disruption of...

Descripción completa

Detalles Bibliográficos
Autores principales: Fekete, E, Allain, T, Buret, A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859127/
http://dx.doi.org/10.1093/jcag/gwab049.014
_version_ 1784654385125523456
author Fekete, E
Allain, T
Buret, A
author_facet Fekete, E
Allain, T
Buret, A
author_sort Fekete, E
collection PubMed
description BACKGROUND: Disruption of intestinal barrier function is important in the pathogenesis of numerous intestinal diseases and can lead to increased intestinal permeability. During infection with the protozoan parasite Giardia duodenalis, intestinal permeability is increased in part due to disruption of the intestinal mucus barrier. Intestinal mucus is composed primarily of the heavily glycosylated MUC2 mucin. Glycosylation of mucins is important for maintaining the structure of the mucus gel, and glycans are key mediators of host-microbe interactions, as they provide binding sites to microbes and can be degraded as a nutrient source. Changes to mucin glycosylation patterns have been noted during intestinal inflammation and bacterial infection, and may contribute to altered intestinal permeability and dysbiosis. We hypothesized that intestinal mucosal glycosylation patterns may be disrupted during Giardia infection, and that this may contribute to Giardia-induced barrier dysfunction. AIMS: Characterize changes to mucosal glycosylation patterns in the small and large intestines during in vivo Giardia infection. METHODS: 3–4 week old C57BL/6 mice were infected with Giardia duodenalis strain GS/M for 7 days. Tissue sections from the jejunum and colon were collected and stained with various fluorescein-coupled lectins (CONA, DBA, PNA, WGA, SNA, UEA-1) and fluorescence was quantified and normalized to tissue area. Quantitative PCR (qPCR) was performed for glycosyltransferase genes in the jejunum and colon. RESULTS: In the jejunum, abundance of N-acetylglucosamine increased upon infection, while sialic acid and fucose abundance were significantly decreased in infected mice compared to controls. Conversely, in the distal colon, mannose and sialic acid abundance increased significantly upon infection. Expression of mucin-associated glycosyltransferase genes was also altered in the small and large intestines of Giardia infected mice. In the jejunums of infected mice, expression of the sulfotransferase Chst4 decreased, while the fucosyltransferase Fut2 and the sialyltransferase St6GalNAc1 increased in comparison to controls. In both the jejunum and distal colon, expression of the core 2 synthase C2GnT1 increased, while expression of the core 1 synthase C1GalT1 was similar between control and infected mice. CONCLUSIONS: Glycosylation patterns and the expression of glycosyltransferase genes are altered in both the small and large intestines of Giardia-infected mice. Disruptions to mucin glycans appear to be regiospecific, suggesting that unique mechanisms are involved in the regulation of mucosal glycosylation during parasitic infection throughout different regions of the gut. These findings uncover a novel mechanism in the pathogenesis of Giardia infection, and may be important in understanding intestinal barrier dysfunction in a variety of different gastrointestinal diseases. FUNDING AGENCIES: CCC
format Online
Article
Text
id pubmed-8859127
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-88591272022-02-22 A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS Fekete, E Allain, T Buret, A J Can Assoc Gastroenterol Poster of Distinction BACKGROUND: Disruption of intestinal barrier function is important in the pathogenesis of numerous intestinal diseases and can lead to increased intestinal permeability. During infection with the protozoan parasite Giardia duodenalis, intestinal permeability is increased in part due to disruption of the intestinal mucus barrier. Intestinal mucus is composed primarily of the heavily glycosylated MUC2 mucin. Glycosylation of mucins is important for maintaining the structure of the mucus gel, and glycans are key mediators of host-microbe interactions, as they provide binding sites to microbes and can be degraded as a nutrient source. Changes to mucin glycosylation patterns have been noted during intestinal inflammation and bacterial infection, and may contribute to altered intestinal permeability and dysbiosis. We hypothesized that intestinal mucosal glycosylation patterns may be disrupted during Giardia infection, and that this may contribute to Giardia-induced barrier dysfunction. AIMS: Characterize changes to mucosal glycosylation patterns in the small and large intestines during in vivo Giardia infection. METHODS: 3–4 week old C57BL/6 mice were infected with Giardia duodenalis strain GS/M for 7 days. Tissue sections from the jejunum and colon were collected and stained with various fluorescein-coupled lectins (CONA, DBA, PNA, WGA, SNA, UEA-1) and fluorescence was quantified and normalized to tissue area. Quantitative PCR (qPCR) was performed for glycosyltransferase genes in the jejunum and colon. RESULTS: In the jejunum, abundance of N-acetylglucosamine increased upon infection, while sialic acid and fucose abundance were significantly decreased in infected mice compared to controls. Conversely, in the distal colon, mannose and sialic acid abundance increased significantly upon infection. Expression of mucin-associated glycosyltransferase genes was also altered in the small and large intestines of Giardia infected mice. In the jejunums of infected mice, expression of the sulfotransferase Chst4 decreased, while the fucosyltransferase Fut2 and the sialyltransferase St6GalNAc1 increased in comparison to controls. In both the jejunum and distal colon, expression of the core 2 synthase C2GnT1 increased, while expression of the core 1 synthase C1GalT1 was similar between control and infected mice. CONCLUSIONS: Glycosylation patterns and the expression of glycosyltransferase genes are altered in both the small and large intestines of Giardia-infected mice. Disruptions to mucin glycans appear to be regiospecific, suggesting that unique mechanisms are involved in the regulation of mucosal glycosylation during parasitic infection throughout different regions of the gut. These findings uncover a novel mechanism in the pathogenesis of Giardia infection, and may be important in understanding intestinal barrier dysfunction in a variety of different gastrointestinal diseases. FUNDING AGENCIES: CCC Oxford University Press 2022-02-21 /pmc/articles/PMC8859127/ http://dx.doi.org/10.1093/jcag/gwab049.014 Text en ڣ The Author(s) 2022. Published by Oxford University Press on behalf of the Canadian Association of Gastroenterology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Poster of Distinction
Fekete, E
Allain, T
Buret, A
A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS
title A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS
title_full A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS
title_fullStr A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS
title_full_unstemmed A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS
title_short A15 GIARDIA DUODENALIS INDUCES REGIOSPECIFIC ALTERATIONS TO INTESTINAL MUCOSAL GLYCOSYLATION PATTERNS
title_sort a15 giardia duodenalis induces regiospecific alterations to intestinal mucosal glycosylation patterns
topic Poster of Distinction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8859127/
http://dx.doi.org/10.1093/jcag/gwab049.014
work_keys_str_mv AT feketee a15giardiaduodenalisinducesregiospecificalterationstointestinalmucosalglycosylationpatterns
AT allaint a15giardiaduodenalisinducesregiospecificalterationstointestinalmucosalglycosylationpatterns
AT bureta a15giardiaduodenalisinducesregiospecificalterationstointestinalmucosalglycosylationpatterns