{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:59:37Z","timestamp":1791331177105,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011372","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000}}],"reference-count":92,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T00:00:00Z","timestamp":1683158400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018-05814"],"award-info":[{"award-number":["2018-05814"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2020-02342"],"award-info":[{"award-number":["2020-02342"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2018-02223"],"award-info":[{"award-number":["2018-02223"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Giardia intestinalis<\/jats:italic> is a non-invasive, protozoan parasite infecting the upper small intestine of most mammals. Symptomatic infections cause the diarrhoeal disease giardiasis in humans and animals, but at least half of the infections are asymptomatic. However, the molecular underpinnings of these different outcomes of the infection are still poorly defined. Here, we studied the early transcriptional response to <jats:italic>G<\/jats:italic>. <jats:italic>intestinalis trophozoites<\/jats:italic>, the disease-causing life-cycle stage, in human enteroid-derived, 2-dimensional intestinal epithelial cell (IEC) monolayers. Trophozoites preconditioned in media that maximise parasite fitness triggered only neglectable inflammatory transcription in the IECs during the first hours of co-incubation. By sharp contrast, \u201cnon-fit\u201d or lysed trophozoites induced a vigorous IEC transcriptional response, including high up-regulation of many inflammatory cytokines and chemokines. Furthermore, \u201cfit\u201d trophozoites could even suppress the stimulatory effect of lysed trophozoites in mixed infections, suggesting active <jats:italic>G<\/jats:italic>. <jats:italic>intestinalis<\/jats:italic> suppression of the IEC response. By dual-species RNA-sequencing, we defined the IEC and <jats:italic>G<\/jats:italic>. <jats:italic>intestinalis<\/jats:italic> gene expression programs associated with these differential outcomes of the infection. Taken together, our results inform on how <jats:italic>G<\/jats:italic>. <jats:italic>intestinalis<\/jats:italic> infection can lead to such highly variable effects on the host, and pinpoints trophozoite fitness as a key determinant of the IEC response to this common parasite.<\/jats:p>","DOI":"10.1371\/journal.ppat.1011372","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T18:09:43Z","timestamp":1683223783000},"page":"e1011372","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Trophozoite fitness dictates the intestinal epithelial cell response to Giardia intestinalis infection"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2507-3375","authenticated-orcid":true,"given":"Jana","family":"Gr\u00fcttner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2865-4455","authenticated-orcid":true,"given":"Jorik M.","family":"van Rijn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2785-4201","authenticated-orcid":true,"given":"Petra","family":"Geiser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1630-4442","authenticated-orcid":true,"given":"Alexandra","family":"Florbrant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6979-9194","authenticated-orcid":true,"given":"Dominic-Luc","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8428-0772","authenticated-orcid":true,"given":"Per M.","family":"Hellstr\u00f6m","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-2859","authenticated-orcid":true,"given":"Magnus","family":"Sundbom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-0803","authenticated-orcid":true,"given":"Mikael E.","family":"Sellin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7392-1746","authenticated-orcid":true,"given":"Staffan G.","family":"Sv\u00e4rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,4]]},"reference":[{"key":"ppat.1011372.ref001","first-page":"447","volume-title":"14, Clinical Microbiology Reviews.","author":"RD Adam","year":"2001"},{"issue":"6","key":"ppat.1011372.ref002","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/nrmicro2317","article-title":"Behind the smile: Cell biology and disease mechanisms of Giardia species","volume":"8","author":"J Ankarklev","year":"2010","journal-title":"Nat Rev Microbiol"},{"issue":"12","key":"ppat.1011372.ref003","doi-asserted-by":"crossref","first-page":"e1001921","DOI":"10.1371\/journal.pmed.1001921","article-title":"World Health Organization Estimates of the Global and Regional Disease Burden of 22 Foodborne Bacterial, Protozoal, and Viral Diseases, 2010: A Data Synthesis","volume":"12","author":"MD Kirk","year":"2015","journal-title":"PLOS Med"},{"issue":"5","key":"ppat.1011372.ref004","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1097\/QCO.0000000000000877","article-title":"Giardia and growth impairment in children in high-prevalence settings: consequence or co-incidence?","volume":"35","author":"M Dougherty","year":"2022","journal-title":"Curr Opin Infect Dis."},{"key":"ppat.1011372.ref005","first-page":"93","volume-title":"Trends in Parasitology","author":"PT Monis","year":"2009"},{"key":"ppat.1011372.ref006","volume-title":"Clinical Infectious Diseases","author":"K Muhsen","year":"2012"},{"issue":"9","key":"ppat.1011372.ref007","doi-asserted-by":"crossref","first-page":"e564","DOI":"10.1016\/S2214-109X(15)00151-5","article-title":"Pathogen-specific burdens of community diarrhoea in developing countries: A multisite birth cohort study (MAL-ED).","volume":"3","author":"JA Platts-Mills","year":"2015","journal-title":"Lancet Glob Heal"},{"issue":"2","key":"ppat.1011372.ref008","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1093\/jpids\/piw082","article-title":"Determinants and impact of Giardia infection in the first 2 years of life in the MAL-ED birth cohort.","volume":"6","author":"ET Rogawski","year":"2017","journal-title":"J Pediatric Infect Dis Soc."},{"issue":"9888","key":"ppat.1011372.ref009","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S0140-6736(13)60844-2","article-title":"Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): A prospective, case-control study.","volume":"382","author":"KL Kotloff","year":"2013","journal-title":"Lancet"},{"key":"ppat.1011372.ref010","article-title":"Advances in understanding Giardia: Determinants and mechanisms of chronic sequelae.","author":"LA Bartelt","year":"2015","journal-title":"F1000Prime Rep."},{"issue":"2","key":"ppat.1011372.ref011","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.pt.2009.11.010","article-title":"Giardiasis\u2014why do the symptoms sometimes never stop","volume":"26","author":"LJ Robertson","year":"2010","journal-title":"Trends Parasitol"},{"issue":"16","key":"ppat.1011372.ref012","doi-asserted-by":"crossref","first-page":"592","DOI":"10.5694\/j.1326-5377.1974.tb71022.x","article-title":"Giardiasis: a common cause of prolonged diarrhoea in adults","volume":"2","author":"T. Heap","year":"1974","journal-title":"Med J Aust."},{"issue":"6","key":"ppat.1011372.ref013","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1093\/cid\/ciw391","article-title":"A Prospective Longitudinal Cohort to Investigate the Effects of Early Life Giardiasis on Growth and All Cause Diarrhea","volume":"63","author":"JR Donowitz","year":"2016","journal-title":"Clin Infect Dis"},{"key":"ppat.1011372.ref014","first-page":"173","article-title":"Pathogenesis and post-infectious complications in giardiasis","author":"T Allain","year":"2020","journal-title":"In: Advances in Parasitology. Academic Press"},{"issue":"1","key":"ppat.1011372.ref015","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12865-017-0190-3","article-title":"Giardia-specific cellular immune responses in post-giardiasis chronic fatigue syndrome","volume":"18","author":"K Hanevik","year":"2017","journal-title":"BMC Immunol"},{"issue":"10","key":"ppat.1011372.ref016","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1093\/cid\/ciu629","article-title":"Irritable bowel syndrome and chronic fatigue 6 years after Giardia infection: A controlled prospective cohort study","volume":"59","author":"K Hanevik","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"1","key":"ppat.1011372.ref017","doi-asserted-by":"crossref","first-page":"48","DOI":"10.3109\/00365529709025062","article-title":"Giardiasis: A histologic analysis of 567 cases","volume":"32","author":"G Oberhuber","year":"1997","journal-title":"Scand J Gastroenterol"},{"issue":"10","key":"ppat.1011372.ref018","doi-asserted-by":"crossref","first-page":"e109087","DOI":"10.1371\/journal.pone.0109087","article-title":"Giardia duodenalis Infection Reduces Granulocyte Infiltration in an In Vivo Model of Bacterial Toxin-Induced Colitis and Attenuates Inflammation in Human Intestinal Tissue","volume":"9","author":"JA Cotton","year":"2014","journal-title":"PLoS One."},{"issue":"4","key":"ppat.1011372.ref019","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.ijpara.2019.12.011","article-title":"Giardia spp. promote the production of antimicrobial peptides and attenuate disease severity induced by attaching and effacing enteropathogens via the induction of the NLRP3 inflammasome","volume":"50","author":"A Manko-Prykhoda","year":"2020","journal-title":"Int J Parasitol"},{"issue":"12","key":"ppat.1011372.ref020","doi-asserted-by":"crossref","first-page":"8204","DOI":"10.1128\/IAI.73.12.8204-8208.2005","article-title":"Giardia lamblia-induced changes in gene expression in differentiated caco-2 human intestinal epithelial cells","volume":"73","author":"K Roxstr\u00f6m-Lindquist","year":"2005","journal-title":"Infect Immun"},{"issue":"12","key":"ppat.1011372.ref021","doi-asserted-by":"crossref","first-page":"e0006120","DOI":"10.1371\/journal.pntd.0006120","article-title":"Characterization of the Giardia intestinalis secretome during interaction with human intestinal epithelial cells: The impact on host cells.","volume":"11","author":"SY Ma\u2019ayeh","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"ppat.1011372.ref022","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fcimb.2022.862211","article-title":"Dual RNA Sequencing Reveals Key Events When Different Giardia Life Cycle Stages Interact With Human Intestinal Epithelial Cells In Vitro","volume":"12","author":"L Rojas","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"9","key":"ppat.1011372.ref023","doi-asserted-by":"crossref","first-page":"e45325","DOI":"10.1371\/journal.pone.0045325","article-title":"Arginine Consumption by the Intestinal Parasite Giardia intestinalis Reduces Proliferation of Intestinal Epithelial Cells","volume":"7","author":"B Stadelmann","year":"2012","journal-title":"PLoS One"},{"issue":"2","key":"ppat.1011372.ref024","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/j.1574-695X.2007.00304.x","article-title":"Caspase-dependent apoptosis of the HCT-8 epithelial cell line induced by the parasite Giardia intestinalis","volume":"51","author":"MA Panaro","year":"2007","journal-title":"FEMS Immunol Med Microbiol"},{"key":"ppat.1011372.ref025","doi-asserted-by":"crossref","first-page":"104315","DOI":"10.1016\/j.micpath.2020.104315","article-title":"Giardia duodenalis induces extrinsic pathway of apoptosis in intestinal epithelial cells through activation of TNFR1 and K63 de-ubiquitination of RIP1 in vitro","volume":"149","author":"L Liu","year":"2020","journal-title":"Microb Pathog"},{"issue":"6","key":"ppat.1011372.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0178647","article-title":"Giardia co-infection promotes the secretion of antimicrobial peptides beta-defensin 2 and trefoil factor 3 and attenuates attaching and effacing bacteria-induced intestinal disease.","volume":"12","author":"A Manko","year":"2017","journal-title":"PLoS One."},{"issue":"2","key":"ppat.1011372.ref027","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.parint.2011.11.002","article-title":"Giardia disrupts the arrangement of tight, adherens and desmosomal junction proteins of intestinal cells","volume":"61","author":"C Maia-Brigag\u00e3o","year":"2012","journal-title":"Parasitol Int"},{"issue":"SEP","key":"ppat.1011372.ref028","article-title":"Giardia\u2019s epithelial cell interaction in vitro: Mimicking asymptomatic infection?","volume":"7","author":"MR Kraft","year":"2017","journal-title":"Front Cell Infect Microbiol."},{"issue":"JUL","key":"ppat.1011372.ref029","article-title":"Responses of the differentiated intestinal epithelial cell line Caco-2 to infection with the giardia intestinalis GS isolate.","volume":"8","author":"SY Ma\u2019ayeh","year":"2018","journal-title":"Front Cell Infect Microbiol."},{"issue":"7","key":"ppat.1011372.ref030","doi-asserted-by":"crossref","first-page":"3673","DOI":"10.1128\/IAI.70.7.3673-3680.2002","article-title":"Strain-dependent induction of enterocyte apoptosis by Giardia lamblia disrupts epithelial barrier function in a caspase-3-dependent manner","volume":"70","author":"AC Chin","year":"2002","journal-title":"Infect Immun"},{"issue":"3","key":"ppat.1011372.ref031","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1136\/gut.2006.100198","article-title":"Effect of chronic Giardia lamblia infection on epithelial transport and barrier function in human duodenum","volume":"56","author":"H Troeger","year":"2007","journal-title":"Gut"},{"issue":"3","key":"ppat.1011372.ref032","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1053\/j.gastro.2021.11.022","article-title":"Dissection of Barrier Dysfunction in Organoid-Derived Human Intestinal Epithelia Induced by Giardia duodenalis","volume":"162","author":"D Holthaus","year":"2022","journal-title":"Gastroenterology"},{"issue":"1","key":"ppat.1011372.ref033","doi-asserted-by":"crossref","DOI":"10.1128\/mbio.00022-22","article-title":"High-Definition DIC Imaging Uncovers Transient Stages of Pathogen Infection Cycles on the Surface of Human Adult Stem Cell-Derived Intestinal Epithelium.","volume":"13","author":"JM van Rijn","year":"2022","journal-title":"MBio."},{"issue":"5","key":"ppat.1011372.ref034","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett\u2019s epithelium","volume":"141","author":"T Sato","year":"2011","journal-title":"Gastroenterology"},{"issue":"7624","key":"ppat.1011372.ref035","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/nature19768","article-title":"Tissue-specific mutation accumulation in human adult stem cells during life","volume":"538","author":"F Blokzijl","year":"2016","journal-title":"Nature"},{"issue":"5","key":"ppat.1011372.ref036","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/stem.1655","article-title":"Adult stem cells in the small intestine are intrinsically programmed with their location-specific function","volume":"32","author":"S Middendorp","year":"2014","journal-title":"Stem Cells"},{"issue":"7244","key":"ppat.1011372.ref037","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"T Sato","year":"2009","journal-title":"Nature"},{"issue":"7","key":"ppat.1011372.ref038","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/s41564-018-0177-8","article-title":"Modelling Cryptosporidium infection in human small intestinal and lung organoids","volume":"3","author":"I Heo","year":"2018","journal-title":"Nat Microbiol"},{"issue":"6306","key":"ppat.1011372.ref039","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1126\/science.aaf5211","article-title":"Replication of human noroviruses in stem cell-derived human enteroids","volume":"353","author":"K Ettayebi","year":"2016","journal-title":"Science (80-)."},{"issue":"4","key":"ppat.1011372.ref040","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00733-18","article-title":"Human intestinal enteroids as a model system of shigella pathogenesis","volume":"87","author":"BJ Koestler","year":"2019","journal-title":"Infect Immun"},{"issue":"4","key":"ppat.1011372.ref041","doi-asserted-by":"crossref","first-page":"e1008498","DOI":"10.1371\/journal.ppat.1008498","article-title":"Intestinal restriction of Salmonella Typhimurium requires caspase-1 and caspase-11 epithelial intrinsic inflammasomes, editor","volume":"16","author":"SM Crowley","year":"2020","journal-title":"PLOS Pathog"},{"issue":"1","key":"ppat.1011372.ref042","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.02684-20","article-title":"Salmonella enterica serovar typhimurium exploits cycling through epithelial cells to colonize human and murine enteroids.","volume":"12","author":"P Geiser","year":"2021","journal-title":"MBio."},{"issue":"15","key":"ppat.1011372.ref043","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.1113\/JP279423","article-title":"Enhancing responsiveness of human jejunal enteroids to host and microbial stimuli","volume":"598","author":"W Ruan","year":"2020","journal-title":"J Physiol"},{"issue":"1","key":"ppat.1011372.ref044","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI117676","article-title":"A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion","volume":"95","author":"HC Jung","year":"1995","journal-title":"J Clin Invest"},{"issue":"6","key":"ppat.1011372.ref045","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/imcb.12550","article-title":"Giardia lamblia regulates the production of proinflammatory cytokines through activating the NOD2\u2013Rip2\u2013ROS signaling pathway in mouse macrophages","volume":"100","author":"X Zhang","year":"2022","journal-title":"Immunol Cell Biol"},{"key":"ppat.1011372.ref046","doi-asserted-by":"crossref","first-page":"694675","DOI":"10.3389\/fcell.2021.694675","article-title":"Giardia duodenalis Induces Proinflammatory Cytokine Production in Mouse Macrophages via TLR9-Mediated p38 and ERK Signaling Pathways","volume":"9","author":"X Pu","year":"2021","journal-title":"Front cell Dev Biol"},{"key":"ppat.1011372.ref047","doi-asserted-by":"crossref","first-page":"913","DOI":"10.3389\/fgene.2020.00913","article-title":"High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions.","volume":"11","author":"D Peirasmaki","year":"2020","journal-title":"Front Genet."},{"issue":"5","key":"ppat.1011372.ref048","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1172\/JCI112162","article-title":"Effects of bile and bile salts on growth and membrane lipid uptake by Giardia lamblia. Possible implications for pathogenesis of intestinal disease","volume":"76","author":"MJG Farthing","year":"1985","journal-title":"J Clin Invest"},{"issue":"3","key":"ppat.1011372.ref049","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1128\/iai.53.3.641-645.1986","article-title":"Biliary lipids support serum-free growth of Giardia lamblia","volume":"53","author":"FD Gillin","year":"1986","journal-title":"Infect Immun"},{"key":"ppat.1011372.ref050","first-page":"4664","volume-title":"Infection and Immunity","author":"HD Lujan","year":"1994"},{"issue":"3","key":"ppat.1011372.ref051","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/gigascience\/giy003","article-title":"Giardia secretome highlights secreted tenascins as a key component of pathogenesis.","volume":"7","author":"A Dubourg","year":"2018","journal-title":"Gigascience."},{"issue":"1","key":"ppat.1011372.ref052","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1080\/21505594.2018.1451284","article-title":"Secreted giardia intestinalis cysteine proteases disrupt intestinal epithelial cell junctional complexes and degrade chemokines","volume":"9","author":"J Liu","year":"2018","journal-title":"Virulence"},{"issue":"5","key":"ppat.1011372.ref053","doi-asserted-by":"crossref","first-page":"110462","DOI":"10.1016\/j.ygeno.2022.110462","article-title":"Comprehensive characterization of Cysteine-rich protein-coding genes of Giardia lamblia and their role during antigenic variation","volume":"114","author":"M Rodr\u00edguez-Walker","year":"2022","journal-title":"Genomics"},{"issue":"11","key":"ppat.1011372.ref054","doi-asserted-by":"crossref","first-page":"3989","DOI":"10.1128\/iai.59.11.3989-3996.1991","article-title":"Variant surface antigens of Giardia lamblia are associated with the presence of a thick cell coat: Thin section and label fracture immunocytochemistry survey","volume":"59","author":"PFP Pimenta","year":"1991","journal-title":"Infect Immun"},{"issue":"5","key":"ppat.1011372.ref055","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/nm.2141","article-title":"Disruption of antigenic variation is crucial for effective parasite vaccine","volume":"16","author":"FD Rivero","year":"2010","journal-title":"Nat Med"},{"issue":"4","key":"ppat.1011372.ref056","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1111\/mmi.12218","article-title":"An ER-directed transcriptional response to unfolded protein stress in the absence of conserved sensor-transducer proteins in Giardia lamblia","volume":"88","author":"C Spycher","year":"2013","journal-title":"Mol Microbiol"},{"issue":"5","key":"ppat.1011372.ref057","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1046\/j.1365-3024.2003.00634.x","article-title":"Mucosal defences against Giardia","volume":"25","author":"L. Eckmann","year":"2003","journal-title":"Parasite Immunol"},{"issue":"2","key":"ppat.1011372.ref058","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1128\/IAI.00718-08","article-title":"Phosphoinositide 3-Kinase-Dependent inhibition of dendritic cell interleukin-12 production by giardia lamblia","volume":"77","author":"JD Kamda","year":"2009","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1011372.ref059","first-page":"1","article-title":"Giardia lamblia Decreases NF-\u03baB p65RelA Protein Levels and Modulates LPS-Induced Pro-Inflammatory Response in Macrophages.","volume":"10","author":"CP Faria","year":"2020","journal-title":"Sci Rep.Dec 1"},{"key":"ppat.1011372.ref060","author":"B Stadelmann","year":"2013","journal-title":"The role of arginine and arginine-metabolizing enzymes during Giardia-host cell interactions in vitro"},{"issue":"2","key":"ppat.1011372.ref061","doi-asserted-by":"crossref","first-page":"548","DOI":"10.4049\/jimmunol.1700824","article-title":"Giardia Infection of the Small Intestine Induces Chronic Colitis in Genetically Susceptible Hosts","volume":"201","author":"SM Dann","year":"2018","journal-title":"J Immunol"},{"issue":"9","key":"ppat.1011372.ref062","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1097\/PAS.0000000000000665","article-title":"Lamblia in Ileal Mucosal Biopsy Specimens May Reveal Giardiasis in Patients With Significantly Inflamed Parasite-free Duodenal Mucosa.","volume":"40","author":"Demonstration of Trophozoites of G","year":"2016","journal-title":"Am J Surg Pathol."},{"issue":"7","key":"ppat.1011372.ref063","doi-asserted-by":"crossref","first-page":"e1006471","DOI":"10.1371\/journal.ppat.1006471","article-title":"Cross-modulation of pathogen-specific pathways enhances malnutrition during enteric co-infection with Giardia lamblia and enteroaggregative Escherichia coli","volume":"13","author":"LA Bartelt","year":"2017","journal-title":"PLOS Pathog"},{"key":"ppat.1011372.ref064","doi-asserted-by":"crossref","first-page":"105944","DOI":"10.1016\/j.intimp.2019.105944","article-title":"Necroptosis in pulmonary macrophages mediates lipopolysaccharide-induced lung inflammatory injury by activating ZBP-1.","volume":"77","author":"ke Du X","year":"2019","journal-title":"Int Immunopharmacol"},{"issue":"7152","key":"ppat.1011372.ref065","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1038\/nature06013","article-title":"DAI (DLM-1\/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response.","volume":"448","author":"A Takaoka","year":"2007","journal-title":"Nature"},{"issue":"15","key":"ppat.1011372.ref066","doi-asserted-by":"crossref","first-page":"7628","DOI":"10.1073\/pnas.93.15.7628","article-title":"Cholesterol starvation induces differentiation of the intestinal parasite Giardia lamblia","volume":"93","author":"HD Luj\u00e1n","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1011372.ref067","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.molbiopara.2009.01.004","article-title":"Lipidomic analysis reveals that phosphatidylglycerol and phosphatidylethanolamine are newly generated phospholipids in an early-divergent protozoan, Giardia lamblia","volume":"165","author":"M Yichoy","year":"2009","journal-title":"Mol Biochem Parasitol"},{"key":"ppat.1011372.ref068","first-page":"267","volume-title":"Parasitology","author":"M Yichoy","year":"2011"},{"issue":"2","key":"ppat.1011372.ref069","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1080\/09674845.2005.11732686","article-title":"Altered lipid parameters in patients infected with Entamoeba histolytica, Entamoeba dispar and Giardia lamblia","volume":"62","author":"D Bansal","year":"2005","journal-title":"Br J Biomed Sci"},{"issue":"2","key":"ppat.1011372.ref070","first-page":"55","article-title":"Mucin2 and Lipid Profile Estimation in Giardia Lamblia Infected Patients: A Case-control Study","volume":"54","author":"RA Alasady","year":"2022","journal-title":"J Commun Dis"},{"issue":"1","key":"ppat.1011372.ref071","doi-asserted-by":"crossref","first-page":"18842","DOI":"10.1038\/s41598-021-98262-8","article-title":"High-fat diet increases the severity of Giardia infection in association with low-grade inflammation and gut microbiota dysbiosis","volume":"11","author":"T Allain","year":"2021","journal-title":"Sci Rep"},{"key":"ppat.1011372.ref072","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.3389\/fcimb.2022.974200","article-title":"Giardial lipid rafts share virulence factors with secreted vesicles and participate in parasitic infection in mice","volume":"12","author":"BI Grajeda","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"5","key":"ppat.1011372.ref073","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1128\/IAI.03118-14","article-title":"The assembly of GM1 glycolipid- and cholesterol-enriched raft-like membrane microdomains is important for giardial encystation","volume":"83","author":"A De Chatterjee","year":"2015","journal-title":"Infect Immun"},{"issue":"1","key":"ppat.1011372.ref074","doi-asserted-by":"crossref","first-page":"e1007468","DOI":"10.1371\/journal.ppat.1007468","article-title":"Increased Programmed Death-Ligand 1 is an Early Epithelial Cell Response to Helicobacter pylori Infection","volume":"15","author":"L Holokai","year":"2019","journal-title":"PLOS Pathog"},{"issue":"1","key":"ppat.1011372.ref075","first-page":"1","article-title":"A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions","volume":"7","author":"G Noel","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"ppat.1011372.ref076","first-page":"1","volume":"7","author":"LM Yonker","year":"2017","journal-title":"Development of a Primary Human Co-Culture Model of Inflamed Airway Mucosa. Sci Rep"},{"issue":"4","key":"ppat.1011372.ref077","doi-asserted-by":"crossref","first-page":"e100300","DOI":"10.15252\/embj.2018100300","article-title":"Long-term expanding human airway organoids for disease modeling","volume":"38","author":"N Sachs","year":"2019","journal-title":"EMBO J"},{"issue":"4","key":"ppat.1011372.ref078","article-title":"Efficient CRISPR\/Cas9-mediated gene disruption in the tetraploid protist","volume":"12","author":"V Hor\u00e1\u010dkov\u00e1","year":"2022","journal-title":"Giardia intestinalis. Open Biol"},{"key":"ppat.1011372.ref079","first-page":"562","volume-title":"Gastroenterology","author":"M Fujii","year":"2019"},{"key":"ppat.1011372.ref080","article-title":"Bacterial detection by NAIP\/NLRC4 elicits prompt contractions of intestinal epithelial cell layers","author":"PS Ventayol","year":"2021","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ppat.1011372.ref081","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/0035-9203(83)90120-7","article-title":"Axenic culture of Giardia lamblia in TYI-S-33 medium supplemented with bile","volume":"77","author":"DB Keister","year":"1983","journal-title":"Trans R Soc Trop Med Hyg"},{"issue":"5812","key":"ppat.1011372.ref082","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/291238a0","article-title":"Aromatic-dependent Salmonella typhimurium are non-virulent and effective as live vaccines","volume":"291","author":"SK Hoiseth","year":"1981","journal-title":"Nature"},{"issue":"2","key":"ppat.1011372.ref083","doi-asserted-by":"crossref","first-page":"e10","DOI":"10.14440\/jbm.2014.36","article-title":"Advanced methods of microscope control using \u03bcManager software.","volume":"1","author":"AD Edelstein","year":"2014","journal-title":"J Biol Methods."},{"key":"ppat.1011372.ref084","first-page":"676","volume-title":"Nature Methods.","author":"J Schindelin","year":"2012"},{"issue":"1","key":"ppat.1011372.ref085","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"1","key":"ppat.1011372.ref086","first-page":"1","article-title":"A chromosome-scale reference genome for Giardia intestinalis WB","volume":"7","author":"F Xu","year":"2020","journal-title":"Sci Data"},{"issue":"1","key":"ppat.1011372.ref087","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"MD Robinson","year":"2009","journal-title":"Bioinformatics"},{"issue":"5","key":"ppat.1011372.ref088","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"ClusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"G Yu","year":"2012","journal-title":"Omi A J Integr Biol"},{"key":"ppat.1011372.ref089","first-page":"1598","article-title":"ggVennDiagram: An Intuitive, Easy-to-Use, and Highly Customizable R Package to Generate Venn Diagram.","volume":"12","author":"C-H Gao","year":"2021","journal-title":"Front Genet."},{"issue":"18","key":"ppat.1011372.ref090","doi-asserted-by":"crossref","first-page":"2847","DOI":"10.1093\/bioinformatics\/btw313","article-title":"Complex heatmaps reveal patterns and correlations in multidimensional genomic data","volume":"32","author":"Z Gu","year":"2016","journal-title":"Bioinformatics"},{"issue":"1","key":"ppat.1011372.ref091","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s12859-018-2246-7","article-title":"Gene length corrected trimmed mean of M-values (GeTMM) processing of RNA-seq data performs similarly in intersample analyses while improving intrasample comparisons.","volume":"19","author":"M Smid","year":"2018","journal-title":"BMC Bioinformatics."},{"issue":"4","key":"ppat.1011372.ref092","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2-\u0394\u0394CT method.","volume":"25","author":"KJ Livak","year":"2001","journal-title":"Methods."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011372","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T00:00:00Z","timestamp":1684195200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011372","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T18:24:05Z","timestamp":1684261445000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011372"}},"subtitle":[],"editor":[{"given":"Alexander R.","family":"Paredez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,5,4]]},"references-count":92,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,5,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011372","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1011372","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,4]]}}}