Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion

Hasnain, Sumaira Z., Dawson, Paul A., Lourie, Rohan, Hutson, Peter, Tong, Hui, Grencis, Richard K., McGuckin, Michael A. and Thornton, David J. (2017) Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion. PLoS Pathogens, 13 2: e1006218. doi:10.1371/journal.ppat.1006218


Author Hasnain, Sumaira Z.
Dawson, Paul A.
Lourie, Rohan
Hutson, Peter
Tong, Hui
Grencis, Richard K.
McGuckin, Michael A.
Thornton, David J.
Title Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion
Formatted title
Immune-driven alterations in mucin sulphation is an important mediator of Trichuris muris helminth expulsion
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7374
1553-7366
Publication date 2017-02-13
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1006218
Open Access Status DOI
Volume 13
Issue 2
Start page e1006218
Total pages 20
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Subject 2405 Parasitology
2404 Microbiology
2403 Immunology
1312 Molecular Biology
1311 Genetics
2406 Virology
Abstract Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T. muris. During chronicity, within the immediate vicinity of the T. muris helminth the goblet cell thecae contained mainly sialylated mucins. In contrast, the goblet cells within the epithelial crypts in the resistant models contained mainly sulphated mucins. Maintained mucin sulphation was promoted by T2-immune responses, in particular IL-13, and contributed to the protective properties of the mucus layer, making it less vulnerable to degradation by T. muris excretory secretory products. Mucin sulphation was markedly reduced in the caecal goblet cells in the sulphate anion transporter-1 (Sat-1) deficient mice. We found that Sat-1 deficient mice were susceptible to chronic infection despite a strong T2-immune response. Lower sulphation levels lead to decreased efficiency of establishment of T. muris infection, independent of egg hatching. This study highlights the complex process by which immune-regulated alterations in mucin glycosylation occur following T. muris infection, which contributes to clearance of parasitic infection.
Formatted abstract
Mucins are heavily glycosylated proteins that give mucus its gel-like properties. Moreover, the glycans decorating the mucin protein core can alter the protective properties of the mucus barrier. To investigate whether these alterations could be parasite-induced we utilized the Trichuris muris (T. muris) infection model, using different infection doses and strains of mice that are resistant (high dose infection in BALB/c and C57BL6 mice) or susceptible (high dose infection in AKR and low dose infection in BALB/c mice) to chronic infection by T. muris. During chronicity, within the immediate vicinity of the T. muris helminth the goblet cell thecae contained mainly sialylated mucins. In contrast, the goblet cells within the epithelial crypts in the resistant models contained mainly sulphated mucins. Maintained mucin sulphation was promoted by TH2-immune responses, in particular IL-13, and contributed to the protective properties of the mucus layer, making it less vulnerable to degradation by T. muris excretory secretory products. Mucin sulphation was markedly reduced in the caecal goblet cells in the sulphate anion transporter-1 (Sat-1) deficient mice. We found that Sat-1 deficient mice were susceptible to chronic infection despite a strong TH2-immune response. Lower sulphation levels lead to decreased efficiency of establishment of T. muris infection, independent of egg hatching. This study highlights the complex process by which immune-regulated alterations in mucin glycosylation occur following T. muris infection, which contributes to clearance of parasitic infection.
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 088785/Z/09/Z
APP1047905
WT100290MA
Institutional Status UQ

 
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