{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:28Z","timestamp":1781308828809,"version":"3.54.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1006649","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T00:00:00Z","timestamp":1507075200000}}],"reference-count":56,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T00:00:00Z","timestamp":1506038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1949\/1"],"award-info":[{"award-number":["GRK1949\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GRK1949\/1"],"award-info":[{"award-number":["GRK1949\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"crossref","award":["GKR1949\/1"],"award-info":[{"award-number":["GKR1949\/1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["PA2792\/2-1"],"award-info":[{"award-number":["PA2792\/2-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1006649","type":"journal-article","created":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T17:38:20Z","timestamp":1506101900000},"page":"e1006649","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":47,"title":["Intestinal helminth infection drives carcinogenesis in colitis-associated colon cancer"],"prefix":"10.1371","volume":"13","author":[{"given":"Eva","family":"Pastille","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Frede","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.","family":"McSorley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Gr\u00e4b","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Adamczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9316-7445","authenticated-orcid":true,"given":"Sebastian","family":"Kollenda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wiebke","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1641-7068","authenticated-orcid":true,"given":"Matthias","family":"Epple","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Buer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick M.","family":"Maizels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6308-0568","authenticated-orcid":true,"given":"Robert","family":"Klopfleisch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2121-2892","authenticated-orcid":true,"given":"Astrid M.","family":"Westendorf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,9,22]]},"reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrc3611","article-title":"Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms","volume":"13","author":"E Elinav","year":"2013","journal-title":"Nat Rev Cancer"},{"issue":"20","key":"ref2","doi-asserted-by":"crossref","first-page":"4794","DOI":"10.3748\/wjg.v22.i20.4794","article-title":"Inflammatory bowel disease and cancer: The role of inflammation, immunosuppression, and cancer treatment","volume":"22","author":"JE Axelrad","year":"2016","journal-title":"World J Gastroenterol"},{"issue":"9573","key":"ref3","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(07)60750-8","article-title":"Inflammatory bowel disease: cause and immunobiology","volume":"369","author":"DC Baumgart","year":"2007","journal-title":"Lancet"},{"issue":"3","key":"ref4","doi-asserted-by":"crossref","first-page":"974","DOI":"10.3748\/wjg.v22.i3.974","article-title":"Disrupted regulatory T cell homeostasis in inflammatory bowel diseases","volume":"22","author":"C Pedros","year":"2016","journal-title":"World J Gastroenterol"},{"issue":"16","key":"ref5","doi-asserted-by":"crossref","first-page":"4258","DOI":"10.1158\/0008-5472.CAN-13-3065","article-title":"Transient ablation of regulatory T cells improves antitumor immunity in colitis-associated colon cancer","volume":"74","author":"E Pastille","year":"2014","journal-title":"Cancer Res"},{"issue":"6","key":"ref6","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri2992","article-title":"Diversity and dialogue in immunity to helminths","volume":"11","author":"JE Allen","year":"2011","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"ref7","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1136\/gut.2004.041749","article-title":"Trichuris suis therapy in Crohn&apos;s disease","volume":"54","author":"RW Summers","year":"2005","journal-title":"Gut"},{"issue":"4","key":"ref8","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1053\/j.gastro.2005.01.005","article-title":"Trichuris suis therapy for active ulcerative colitis: a randomized controlled trial","volume":"128","author":"RW Summers","year":"2005","journal-title":"Gastroenterology"},{"issue":"11","key":"ref9","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1111\/pim.12003","article-title":"Heligmosmoides polygyrus fourth stages induce protection against DSS-induced colitis and change opioid expression in the intestine","volume":"34","author":"K Donskow-Lysoniewska","year":"2012","journal-title":"Parasite Immunol"},{"issue":"8","key":"ref10","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1002\/ibd.22858","article-title":"Heligmosomoides polygyrus abrogates antigen-specific gut injury in a murine model of inflammatory bowel disease","volume":"18","author":"J Leung","year":"2012","journal-title":"Inflamm Bowel Dis"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"7368","DOI":"10.4049\/jimmunol.174.11.7368","article-title":"Neutralizing anti-IL-10 antibody blocks the protective effect of tapeworm infection in a murine model of chemically induced colitis","volume":"174","author":"MM Hunter","year":"2005","journal-title":"J Immunol"},{"issue":"4","key":"ref12","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1053\/j.gastro.2007.01.038","article-title":"Helminth infection enhances disease in a murine TH2 model of colitis","volume":"132","author":"MM Hunter","year":"2007","journal-title":"Gastroenterology"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"2850","DOI":"10.2353\/ajpath.2010.100537","article-title":"Exacerbation of oxazolone colitis by infection with the helminth Hymenolepis diminuta: involvement of IL-5 and eosinophils","volume":"177","author":"A Wang","year":"2010","journal-title":"Am J Pathol"},{"issue":"7","key":"ref14","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.3748\/wjg.v20.i7.1797","article-title":"Increased susceptibility to Trichuris muris infection and exacerbation of colitis in Mdr1a-\/- mice","volume":"20","author":"EK Bhardwaj","year":"2014","journal-title":"World J Gastroenterol"},{"key":"ref15","article-title":"Helminth-induced alterations of the gut microbiota exacerbate bacterial colitis","author":"C Su","year":"2017","journal-title":"Mucosal Immunol"},{"issue":"3","key":"ref16","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1046\/j.1365-2796.2000.00742.x","article-title":"Infections as a major preventable cause of human cancer","volume":"248","author":"H Kuper","year":"2000","journal-title":"J Intern Med"},{"issue":"12","key":"ref17","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.1002\/ijc.30028","article-title":"Carcinogenesis associated with parasites other than Schistosoma, Opisthorchis and Clonorchis: A systematic review","volume":"138","author":"C Machicado","year":"2016","journal-title":"Int J Cancer"},{"issue":"10","key":"ref18","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.pt.2012.07.006","article-title":"The tumorigenic liver fluke Opisthorchis viverrini\u2014multiple pathways to cancer","volume":"28","author":"B Sripa","year":"2012","journal-title":"Trends Parasitol"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/mi.2015.73","article-title":"Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths","volume":"9","author":"KA Smith","year":"2016","journal-title":"Mucosal Immunol"},{"issue":"5","key":"ref20","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1128\/IAI.01233-07","article-title":"Functional analysis of effector and regulatory T cells in a parasitic nematode infection","volume":"76","author":"S Rausch","year":"2008","journal-title":"Infect Immun"},{"issue":"3","key":"ref21","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1084\/jem.20031562","article-title":"Developmental stage, phenotype, and migration distinguish naive- and effector\/memory-like CD4+ regulatory T cells","volume":"199","author":"J Huehn","year":"2004","journal-title":"J Exp Med"},{"issue":"4","key":"ref22","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.4049\/jimmunol.1201457","article-title":"Heligmosomoides polygyrus bakeri infection activates colonic Foxp3+ T cells enhancing their capacity to prevent colitis","volume":"191","author":"L Hang","year":"2013","journal-title":"J Immunol"},{"issue":"2","key":"ref23","first-page":"483","article-title":"Dose-dependent promoting effect of dextran sodium sulfate on mouse colon carcinogenesis initiated with azoxymethane","volume":"20","author":"R Suzuki","year":"2005","journal-title":"Histol Histopathol"},{"issue":"6","key":"ref24","doi-asserted-by":"crossref","first-page":"e6026","DOI":"10.1371\/journal.pone.0006026","article-title":"Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility","volume":"4","author":"JM Uronis","year":"2009","journal-title":"PLoS One"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"G109","DOI":"10.1152\/ajpgi.00214.2005","article-title":"T cell-induced inflammation of the small and large intestine in immunodeficient mice","volume":"290","author":"DV Ostanin","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"1","key":"ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1556\/1886.2015.00048","article-title":"Targeting Antigens to Dec-205 on Dendritic Cells Induces Immune Protection in Experimental Colitis in Mice","volume":"6","author":"M Wadwa","year":"2016","journal-title":"Eur J Microbiol Immunol (Bp)"},{"issue":"5","key":"ref27","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"MF Neurath","year":"2014","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"ref28","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.ccr.2009.01.001","article-title":"IL-6 and Stat3 are required for survival of intestinal epithelial cells and development of colitis-associated cancer","volume":"15","author":"S Grivennikov","year":"2009","journal-title":"Cancer Cell"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1172\/JCI34261","article-title":"Helminth infections: the great neglected tropical diseases","volume":"118","author":"PJ Hotez","year":"2008","journal-title":"J Clin Invest"},{"issue":"6","key":"ref30","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/S1470-2045(12)70137-7","article-title":"Global burden of cancers attributable to infections in 2008: a review and synthetic analysis","volume":"13","author":"C de Martel","year":"2012","journal-title":"Lancet Oncol"},{"issue":"6","key":"ref31","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.4049\/jimmunol.1000941","article-title":"Heligmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity","volume":"185","author":"L Hang","year":"2010","journal-title":"J Immunol"},{"issue":"10","key":"ref32","doi-asserted-by":"crossref","first-page":"4772","DOI":"10.1128\/IAI.00744-07","article-title":"Anti-Inflammatory mechanisms of enteric Heligmosomoides polygyrus infection against trinitrobenzene sulfonic acid-induced colitis in a murine model","volume":"76","author":"TL Sutton","year":"2008","journal-title":"Infect Immun"},{"issue":"7","key":"ref33","doi-asserted-by":"crossref","first-page":"4557","DOI":"10.4049\/jimmunol.178.7.4557","article-title":"Infection with a helminth parasite prevents experimental colitis via a macrophage-mediated mechanism","volume":"178","author":"P Smith","year":"2007","journal-title":"J Immunol"},{"issue":"11","key":"ref34","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1002\/ibd.21629","article-title":"Hookworm products ameliorate dextran sodium sulfate-induced colitis in BALB\/c mice","volume":"17","author":"GG Cancado","year":"2011","journal-title":"Inflamm Bowel Dis"},{"issue":"5","key":"ref35","doi-asserted-by":"crossref","first-page":"e96454","DOI":"10.1371\/journal.pone.0096454","article-title":"Excretory\/secretory products from Trichinella spiralis adult worms ameliorate DSS-induced colitis in mice","volume":"9","author":"X Yang","year":"2014","journal-title":"PLoS One"},{"issue":"4","key":"ref36","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF02285159","article-title":"Dextran sulfate sodium (DSS) induced experimental colitis in immunodeficient mice: effects in CD4(+) -cell depleted, athymic and NK-cell depleted SCID mice","volume":"45","author":"LG Axelsson","year":"1996","journal-title":"Inflamm Res"},{"issue":"5","key":"ref37","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1538\/expanim.50.387","article-title":"Dextran sodium sulfate-induced colitis in germ-free IQI\/Jic mice","volume":"50","author":"S Kitajima","year":"2001","journal-title":"Exp Anim"},{"issue":"1","key":"ref38","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1111\/imr.12039","article-title":"CD4(+) T-cell subsets in intestinal inflammation","volume":"252","author":"M Shale","year":"2013","journal-title":"Immunol Rev"},{"issue":"7","key":"ref39","doi-asserted-by":"crossref","first-page":"e69936","DOI":"10.1371\/journal.pone.0069936","article-title":"New perspective on dextran sodium sulfate colitis: antigen-specific T cell development during intestinal inflammation","volume":"8","author":"ME Morgan","year":"2013","journal-title":"PLoS One"},{"issue":"8","key":"ref40","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/ibd.20148","article-title":"Il-6 signaling in inflammatory bowel disease: pathophysiological role and clinical relevance","volume":"13","author":"J Mudter","year":"2007","journal-title":"Inflamm Bowel Dis"},{"issue":"5","key":"ref41","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/75068","article-title":"Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: evidence in crohn disease and experimental colitis in vivo","volume":"6","author":"R Atreya","year":"2000","journal-title":"Nat Med"},{"issue":"8","key":"ref42","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1097\/MIB.0b013e318286fa1c","article-title":"TH17 cell induction and effects of IL-17A and IL-17F blockade in experimental colitis","volume":"19","author":"EG Wedebye Schmidt","year":"2013","journal-title":"Inflamm Bowel Dis"},{"issue":"5","key":"ref43","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1189\/jlb.0207118","article-title":"Crucial pathophysiological role of CXCR2 in experimental ulcerative colitis in mice","volume":"82","author":"P Buanne","year":"2007","journal-title":"J Leukoc Biol"},{"issue":"4","key":"ref44","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1084\/jem.20052124","article-title":"CXCL1 induced by prostaglandin E2 promotes angiogenesis in colorectal cancer","volume":"203","author":"D Wang","year":"2006","journal-title":"J Exp Med"},{"issue":"7","key":"ref45","doi-asserted-by":"crossref","first-page":"e0005817","DOI":"10.1371\/journal.pntd.0005817","article-title":"Mixed Th1 and Th2 Mycobacterium tuberculosis-specific CD4 T cell responses in patients with active pulmonary tuberculosis from Tanzania","volume":"11","author":"P Amelio","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"ref46","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1017\/S0022149X11000460","article-title":"Immune monitoring of Trichuris suis egg therapy in multiple sclerosis patients","volume":"86","author":"F Benzel","year":"2012","journal-title":"J Helminthol"},{"issue":"1","key":"ref47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijpara.2016.08.007","article-title":"Concomitant helminth infection downmodulates the Vaccinia virus-specific immune response and potentiates virus-associated pathology","volume":"47","author":"PH Gazzinelli-Guimaraes","year":"2017","journal-title":"Int J Parasitol"},{"issue":"3","key":"ref48","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.1128\/IAI.01236-07","article-title":"Coinfection with Heligmosomoides polygyrus fails to establish CD8+ T-cell immunity against Toxoplasma gondii","volume":"76","author":"IA Khan","year":"2008","journal-title":"Infect Immun"},{"issue":"5","key":"ref49","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.immuni.2014.04.010","article-title":"Bystander chronic infection negatively impacts development of CD8(+) T cell memory","volume":"40","author":"E Stelekati","year":"2014","journal-title":"Immunity"},{"issue":"4","key":"ref50","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/0014-4894(91)90074-7","article-title":"Heligmosomoides polygyrus: CD4+ but not CD8+ T cells regulate the IgE response and protective immunity in mice","volume":"73","author":"JF Urban Jr.","year":"1991","journal-title":"Exp Parasitol"},{"issue":"10","key":"ref51","doi-asserted-by":"crossref","first-page":"e78034","DOI":"10.1371\/journal.pone.0078034","article-title":"Colitis promotes adaptation of an intestinal nematode: a Heligmosomoides polygyrus mouse model system","volume":"8","author":"K Donskow-Lysoniewska","year":"2013","journal-title":"PLoS One"},{"issue":"7","key":"ref52","doi-asserted-by":"crossref","first-page":"950","DOI":"10.1136\/gut.2004.061283","article-title":"In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy","volume":"54","author":"C Becker","year":"2005","journal-title":"Gut"},{"issue":"60","key":"ref53","article-title":"Investigating intestinal inflammation in DSS-induced model of IBD","author":"JJ Kim","year":"2012","journal-title":"J Vis Exp"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.jconrel.2015.12.021","article-title":"Colonic gene silencing using siRNA-loaded calcium phosphate\/PLGA nanoparticles ameliorates intestinal inflammation in vivo","volume":"222","author":"A Frede","year":"2016","journal-title":"J Control Release"},{"issue":"98","key":"ref55","first-page":"e52412","article-title":"Cultivation of Heligmosomoides polygyrus: an immunomodulatory nematode parasite and its secreted products","author":"CJ Johnston","year":"2015","journal-title":"J Vis Exp"},{"issue":"1","key":"ref56","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1002\/eji.201343746","article-title":"IL-6 controls susceptibility to helminth infection by impeding Th2 responsiveness and altering the Treg phenotype in vivo","volume":"44","author":"KA Smith","year":"2014","journal-title":"Eur J Immunol"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1006649","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,10,4]],"date-time":"2017-10-04T00:00:00Z","timestamp":1507075200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1006649","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T07:43:16Z","timestamp":1589010196000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1006649"}},"subtitle":[],"editor":[{"given":"P'ng","family":"Loke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,9,22]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1006649","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1006649","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,22]]}}}