serine protease(s) secreted by the nematode trichuris muris degrade the mucus barrier丝氨酸蛋白酶(s)分泌的线虫鞭缪里斯降低粘液屏障.pdfVIP

Serine Protease(s) Secreted by the Nematode Trichuris muris Degrade the Mucus Barrier 1,2,3 1 2 3 Sumaira Z. Hasnain *, Michael A. McGuckin , Richard K. Grencis , David J. Thornton * 1 Immunity, Infection and Inflammation, Mater Medical Research Institute, Brisbane, Australia, 2 Manchester Immunology Group, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom, 3 Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom Abstract The polymeric mucin component of the intestinal mucus barrier changes during nematode infection to provide not only physical protection but also to directly affect pathogenic nematodes and aid expulsion. Despite this, the direct interaction of the nematodes with the mucins and the mucus barrier has not previously been addressed. We used the well-established Trichuris muris nematode model to investigate the effect on mucins of the complex mixture of immunogenic proteins secreted by the nematode called excretory/secretory products (ESPs). Different regimes of T. muris infection were used to simulate chronic (low dose) or acute (high dose) infection. Mucus/mucins isolated from mice and from the human intestinal cell line, LS174T, were treated with ESPs. We demonstrate that serine protease(s) secreted by the nematode have the ability to change the properties of the mucus barrier, making it more porous by degrading the mucin component of the mucus gel. Specifically, the serine protease(s) acted on the N-terminal polymerising domain of the major intestinal mucin Muc2, resulting in depolymerisation of Muc2 polyme