{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T05:37:50Z","timestamp":1776749870832,"version":"3.51.2"},"reference-count":71,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,30]],"date-time":"2022-09-30T00:00:00Z","timestamp":1664496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Programa de Recursos Fiscales para Investigaci\u00f3n from Instituto Nacional de Pediatr\u00eda","award":["2019\/062"],"award-info":[{"award-number":["2019\/062"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Beyond the problem in public health that protist-generated diseases represent, understanding the variety of mechanisms used by these parasites to interact with the human immune system is of biological and medical relevance. Giardia lamblia is an early divergent eukaryotic microorganism showing remarkable pathogenic strategies for evading the immune system of vertebrates. Among various multifunctional proteins in Giardia, arginine deiminase is considered an enzyme that plays multiple regulatory roles during the life cycle of this parasite. One of its most important roles is the crosstalk between the parasite and host. Such a molecular \u201cchat\u201d is mediated in human cells by membrane receptors called Toll-like receptors (TLRs). Here, we studied the importance of the 3D structure of giardial arginine deiminase (GlADI) to immunomodulate the human immune response through TLRs. We demonstrated the direct effect of GlADI on human TLR signaling. We predicted its mode of interaction with TLRs two and four by using the AlphaFold-predicted structure of GlADI and molecular docking. Furthermore, we showed that the immunomodulatory capacity of this virulent factor of Giardia depends on the maintenance of its 3D structure. Finally, we also showed the influence of this enzyme to exert specific responses on infant-like dendritic cells.<\/jats:p>","DOI":"10.3390\/ijms231911552","type":"journal-article","created":{"date-parts":[[2022,10,8]],"date-time":"2022-10-08T22:19:27Z","timestamp":1665267567000},"page":"11552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Giardial Arginine Deiminase Participates in Giardia-Host Immunomodulation in a Structure-Dependent Fashion via Toll-like Receptors"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7468-3420","authenticated-orcid":false,"given":"Cynthia","family":"Fern\u00e1ndez-Lainez","sequence":"first","affiliation":[{"name":"Laboratorio de Errores Innatos del Metabolismo y Tamiz, Instituto Nacional de Pediatria, Ciudad de M\u00e9xico 04530, Mexico"},{"name":"Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, 9700 Groningen, The Netherlands"},{"name":"Posgrado en Ciencias Biol\u00f3gicas, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Ciudad de M\u00e9xico 04510, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-8089","authenticated-orcid":false,"given":"Ignacio","family":"de la Mora-de la Mora","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomoleculas y Salud Infantil, Instituto Nacional de Pediatria, Ciudad de M\u00e9xico 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2058-5707","authenticated-orcid":false,"given":"Sergio","family":"Enr\u00edquez-Flores","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomoleculas y Salud Infantil, Instituto Nacional de Pediatria, Ciudad de M\u00e9xico 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Itzhel","family":"Garc\u00eda-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomoleculas y Salud Infantil, Instituto Nacional de Pediatria, Ciudad de M\u00e9xico 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"Flores-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomoleculas y Salud Infantil, Instituto Nacional de Pediatria, Ciudad de M\u00e9xico 04530, Mexico"},{"name":"CONACYT-Instituto Nacional de Pediatria, Secretaria de Salud, Ciudad de M\u00e9xico 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pedro","family":"Guti\u00e9rrez-Castrell\u00f3n","sequence":"additional","affiliation":[{"name":"Hospital General Dr. Manuel Gea Gonz\u00e1lez, Ciudad de M\u00e9xico 14080, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9618-2408","authenticated-orcid":false,"given":"Paul","family":"de Vos","sequence":"additional","affiliation":[{"name":"Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, 9700 Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0470-1069","authenticated-orcid":false,"given":"Gabriel","family":"L\u00f3pez-Vel\u00e1zquez","sequence":"additional","affiliation":[{"name":"Laboratorio de Biomoleculas y Salud Infantil, Instituto Nacional de Pediatria, Ciudad de M\u00e9xico 04530, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1111\/j.1365-2982.2007.00988.x","article-title":"Increased visceral sensitivity in Giardia-induced postinfectious irritable bowel syndrome and functional dyspepsia. 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