{"doi":"10.1016/j.ajpath.2017.07.009","title":"Cysteine Protease–Dependent Mucous Disruptions and Differential Mucin Gene Expression in Giardia duodenalis Infection","abstract":null,"journal":"The American Journal of Pathology","year":2017,"id":600176,"datarank":0.6307038929086449,"base_score":4.204692619390966,"endowment":4.204692619390966,"self_citation_contribution":0.6307038929086449,"citation_network_contribution":0.0,"self_endowment_contribution":0.6307038929086449,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":66,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1538474,"name":"Jean-Paul Motta","orcid":null,"position":1,"is_corresponding":false},{"id":1538477,"name":"Elena Fekete","orcid":null,"position":2,"is_corresponding":false},{"id":1538479,"name":"France Moreau","orcid":null,"position":3,"is_corresponding":false},{"id":1538481,"name":"Kris Chadee","orcid":"0000-0003-2636-557X","position":4,"is_corresponding":false},{"id":1538482,"name":"Andre G. Buret","orcid":null,"position":5,"is_corresponding":false},{"id":1538472,"name":"Christina B. Amat","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Cysteine Protease–Dependent Mucous Disruptions and Differential Mucin Gene Expression in Giardia duodenalis Infection","abstract":"The intestinal mucous layer provides a critical host defense against pathogen exposure and epithelial injury, yet little is known about how enteropathogens may circumvent this physiologic barrier. Giardia duodenalis is a small intestinal parasite responsible for diarrheal disease and chronic postinfectious illness. This study reveals a complex interaction at the surface of epithelial cells, between G. duodenalis and the intestinal mucous layer. Here, we reveal mechanisms whereby G. duodenalis evades and disrupts the first line of host defense by degrading human mucin-2 (MUC2), depleting mucin stores and inducing differential gene expression in the mouse small and large intestines. Human colonic biopsy specimens exposed to G. duodenalis were depleted of mucus, and in vivo mice infected with G. duodenalis had a thinner mucous layer and demonstrated differential Muc2 and Muc5ac mucin gene expression. Infection in Muc2<sup>-/-</sup> mice elevated trophozoite colonization in the small intestine and impaired weight gain. In vitro, human LS174T goblet-like cells were depleted of mucus and had elevated levels of MUC2 mRNA expression after G. duodenalis exposure. Importantly, the cysteine protease inhibitor E64 prevented mucous degradation, mucin depletion, and the increase in MUC2 expression. This article describes a novel role for Giardia's cysteine proteases in pathogenesis and how Giardia's disruptions of the mucous barrier facilitate bacterial translocation that may contribute to the onset and propagation of disease.","is_dataset_classified":null,"base_score":4.204692619390966,"endowment":4.204692619390966,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28823873","pmcid":null,"openalex_id":"https://openalex.org/W2745866105","authors":[],"funders":[{"funder_name":"Crohn&apos;s and Colitis Canada","grant_id":"20142017","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"413888-2012","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"183681-2011","title":null},{"funder_name":"Natural Sciences and Engineering Research Council of Canada","grant_id":"unidentified","title":"unidentified"},{"funder_name":"University of Calgary","grant_id":"","title":null},{"funder_name":"Canadian Association of Gastroenterology","grant_id":"","title":null},{"funder_name":"Alberta Innovates - Health Solutions","grant_id":"","title":null}],"total_grants":7,"fwci":4.5639,"citation_percentile":0.9544998,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":5},{"year":2019,"count":9},{"year":2020,"count":9},{"year":2021,"count":11},{"year":2022,"count":12},{"year":2023,"count":11},{"year":2024,"count":2},{"year":2025,"count":5},{"year":2026,"count":1}],"oa_status":"bronze","license":"Elsevier Non-Commercial","oa_locations":[{"url":"http://ajp.amjpathol.org/article/S0002944017304327/pdf","host_type":"journal"},{"url":"http://ajp.amjpathol.org/article/S0002944017304327/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0002944017304327?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0002944017304327?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.ajpath.2017.07.009","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28823873","host_type":"repository"},{"url":"https://hal.science/hal-04870615","host_type":"repository"},{"url":"https://dx.doi.org/10.1016/j.ajpath.2017.07.009","host_type":""}],"fields_of_study":["Parasitic Infections and Diagnostics","Amoebic Infections and Treatments","Parasites and Host Interactions","0301 basic medicine","0303 health sciences","03 medical and health sciences","Animals","Bacterial Translocation","Cysteine Proteases","Epithelial Cells","Female","Giardia lamblia","Giardiasis","Humans","Intestinal Mucosa","Male","Mice","Mucins","Mucus"],"mesh_terms":["Animals","Epithelial Cells","Female","Giardiasis","Humans","Intestinal Mucosa","Male","Mucins","Mucus","Giardia lamblia","Bacterial Translocation","Mice","Cysteine Proteases"],"keywords":["Mucin","Biology","Mucus","Mucin 2","Microbiology","Proteases","Intestinal mucosa","Cysteine protease","Immunology","Gene expression","Gene","Medicine","Enzyme","Giardiasis","Male","Mucins","Epithelial Cells","Mice","Cysteine Proteases","Bacterial Translocation","Animals","Humans","Female","Giardia lamblia"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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