Altered Mucosal Glycosylation Patterns during Giardia spp. Infection are Time‐Dependent and Tissue‐Specific

Abstract

IntroductionGlycosylation of intestinal mucin proteins is critical for intestinal barrier function and host‐microbe interactions. Altered mucosal glycosylation patterns have been associated with numerous intestinal diseases and may contribute to dysbiosis and an increase in intestinal permeability. Disruption of intestinal mucus has been described during infection with the protozoan parasite Giardia duodenalis, and may contribute to intestinal mucosal barrier dysfunction and dysbiosis during acute and chronic infection. Little is currently known about the role of mucin glycan alteration in the pathogenesis of Giardia or other enteric infections. The aim of this study was to determine if mucosal glycosylation patterns are altered during Giardia infection.Methods3‐4‐week‐old C57BL/6 mice were infected with Giardia muris for 2 or 7 days, or with Giardia duodenalis isolate GSM for 7 days. Jejunum and colon sections were collected and stained with various fluorescein‐coupled lectins, and quantitative PCR was performed for mucin and mucin‐associated glycosyltransferase gene expression.ResultsDuring early infection, at day 2 post‐infection (PI), fucose and sialic acid abundance was increased in the jejunums of G. muris infected mice in comparison to uninfected mice. Expression of the fucosyltransferase Fut2 and the sialyltransferase St6GalNAc1 were similar between controls and infected mice. Expression of the sulfotransferase Chst4 was decreased in both the jejunums and colons upon infection.At day 7 PI, when trophozoite burden was maximal in the small intestine, the abundance of fucose and sialic acid was significantly decreased in the jejunums of both G. muris and G. duodenalis infected mice. The expression of Fut2 and St6GalNAc1 was increased in infected mice compared to controls. Both fucose abundance and Fut2 expression were similar between control and infected mice in the colon, while sialic acid abundance increased and expression of St6GalNAc1 decreased in the colon upon infection. Expression of the sulfotransferase Chst4 was decreased in infected mice in the jejunum, and similar to control levels in the colon.ConclusionsGlycosylation patterns and the expression of mucin‐associated glycosyltransferase genes are altered in the intestines upon Giardia spp. infection. These alterations are time‐dependent as well as tissue‐specific, occurring in the small intestine, where Giardia colonization occurs, and in the large intestine where no active trophozoites are present during infection. These effects are isolate non‐specific and may contribute to disruption of intestinal barrier function and dysbiosis during Giardia infections, as well as during numerous enteric infections in which mucus disruption is implicated in disease pathogenesis.