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Antimicrobial factors, including lysozymes and \u03b2-defensins, are often embedded in luminal glycosylated colonic Muc2 mucin secreted by goblet cells that form the protective mucus layer critical for gut homeostasis and pathogen invasion. In this study, we investigated ileal innate immunity against<jats:named-content content-type=\"genus-species\">Entamoeba histolytica<\/jats:named-content>, the causative agent of intestinal amebiasis, by inoculating parasites in closed ileal loops in<jats:italic>Muc2<jats:sup>+\/+<\/jats:sup><\/jats:italic>and<jats:italic>Muc2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>littermates and quantifying Paneth cell localization (lysozyme expression) and function (Crp secretion). Relative to<jats:italic>Muc2<jats:sup>+\/+<\/jats:sup><\/jats:italic>littermates,<jats:italic>Muc2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>littermates showed a disorganized mislocalization of Paneth cells that was diffusely distributed, with elevated lysozyme secretion in the crypts and on villi in response to<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>. Inhibition of<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>Gal\/GalNAc lectin (Gal-lectin) binding with exogenous galactose and<jats:italic>Entamoeba histolytica<\/jats:italic>cysteine proteinase 5 (<jats:italic>Eh<\/jats:italic>CP5)-negative<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>had no effect on parasite-induced erratic Paneth cell lysozyme synthesis. Although the basal ileal expression of<jats:italic>Crp<\/jats:italic>genes was unaffected in<jats:italic>Muc2<jats:sup>\u2212\/\u2212<\/jats:sup><\/jats:italic>mice in response to<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>, there was a robust release of proinflammatory cytokines and Crp peptide secretions in luminal exudates that was also present in the colon. Interestingly,<jats:named-content content-type=\"genus-species\">E. histolytica<\/jats:named-content>-secreted cysteine proteinases cleaved the proregion of Crp4 but not the active form. These findings define Muc2 mucin as an essential component of ileal barrier function that regulates the localization and function of Paneth cells critical for host defense against microbes.<\/jats:p>","DOI":"10.1128\/iai.00208-18","type":"journal-article","created":{"date-parts":[[2018,4,18]],"date-time":"2018-04-18T09:03:06Z","timestamp":1524042186000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Entamoeba histolytica Alters Ileal Paneth Cell Functions in Intact and Muc2 Mucin Deficiency"],"prefix":"10.1128","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-7673","authenticated-orcid":false,"given":"Eduardo R.","family":"Cobo","sequence":"first","affiliation":[{"name":"Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, 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