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Abstract

The glycosylation alterations of mouse small intestinal mucins during a 12-day infectious cycle caused by the parasite Nippostrongylus brasiliensis have been studied. The guanidinium chloride insoluble mucins were isolated at day 0 to 12 from the small intestine of infected and non-infected C57BL/6 mice. The O-linked oligosaccharides were released by reductive beta-elimination from the mucins and separated into neutral, sialylated and sulfated fractions. All fractions were analyzed by monosaccharide composition analysis and the neutral oligosaccharides were structurally characterized by gas chromatography/mass spectrometry. Two oligosaccharides containing blood group H-type epitopes (Fucalpha1-2Gal-) were transiently expressed with a maximum at day 6. Additional oligosaccharides with the common structure HexNAc-Gal-3GalNAcol were transiently induced with a maximum at day 10. Northern blot analysis on total RNA showed a transient expression at day 4-6 of the Fut2 gene encoding a Fucalpha1-2 fucosyltransferase, probably responsible for the detected blood group H-type epitopes. Comparisons with the corresponding infection in rat studied previously, revealed structurally different alterations, although occurring as transient events in both species. Both showed an induced blood group-type transferase halfway through the infection (a blood group A transferase in rat) and an induced transferase adding a terminal GalNAc (to a sialic acid- containing epitope in rat) towards the end of the infection. These differences between closely related species suggest rapid evolutionary alterations in glycosyltransferase expression.

Normalization of Host Intestinal Mucus Layers Requires Long-Term Microbial Colonization

“…Mucin O -glycosylation has also been previously shown to be a dynamic system and glycan patterns are commonly altered as secondary effects to infection and inflammation. The Fut2 enzyme is known to be upregulated in the mouse small intestine upon infection and in cystic fibrosis (Bry et al, 1996; Holmen et al, 2002; Thomsson et al, 2002). Patients with ulcerative colitis have been shown to have a transient altered glycosylation of MUC2 that was reversed to normal when the patient went into remission (Holmén Larsson et al, 2011).…”

Infection with the gastrointestinal nematode Ostertagia ostertagi in cattle affects mucus biosynthesis in the abomasum

“…The increased levels of fucose in the tissue during infection are consistent with the observed increase in transcription levels of FUT2 and FUT4 , coding for enzymes transfering Fuc α-1,2 and Fuc α-1,3 respectively, on mucins. Similarly in the small intestine of rats infected with N. brasiliensis , an induced fucosylation, due to an upregulation of Fut2 gene expression, has been reported [38]. Disulphide isomerases are a family of enzymes that play an important role in the process of disulphide bond formation of gel forming mucins [39,40].…”

A sticky end for gastrointestinal helminths; the role of the mucus barrier

“…spiralis , T. muris and H . polygyrus 76, 77, 78, 79. It has yet to be determined whether these changes occur as a result of the inflammatory environment or to resolve the infection; clearly more research is required to define the precise role of mucin glycans.…”

“…It has yet to be determined whether these changes occur as a result of the inflammatory environment or to resolve the infection; clearly more research is required to define the precise role of mucin glycans. Most of our current understanding of the central role that mucin glycosylation plays during inflammatory threat has come from challenging rodents with infectious agents,71, 77, 78 and there are data to suggest that during GI nematode infections, there are multiple changes in the expression of glycosyltransferases, the enzymes responsible for the synthesis of the glycan chains 75. Yamauchi et al77 have demonstrated that by day 2‐3 of T. spiralis infection, there is an increase in α‐2‐3‐sialyltransferase IV.…”