{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:46:42Z","timestamp":1787014002765,"version":"build-2736575974"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2014,1,3]],"date-time":"2014-01-03T00:00:00Z","timestamp":1388707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["A94\/06"],"award-info":[{"award-number":["A94\/06"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else Kr\u00f6ner-Fresenius-Stiftung","doi-asserted-by":"publisher","award":["A47\/2010"],"award-info":[{"award-number":["A47\/2010"]}],"id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,1,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>Fatalities from schistosome infections arise due to granulomatous, immune-mediated responses to eggs that become trapped in host tissues. Schistosome-specific immune responses are characterized by initial T helper type 1 (Th1) responses and our previous studies demonstrated that myeloid differentiation primary response gene 88 (Myd88)-deficient mice failed to initiate such responses in vivo. Paradoxically, schistosomal antigens fail to stimulate innate cells to release proinflammatory cytokines in vitro. Since Schistosoma mansoni infection is an intestinal disease, we hypothesized that commensal bacteria could act as bystander activators of the intestinal innate immune system to instigate Th1 responses. Using a broad spectrum of orally administered antibiotics and anti-mycotics we analysed schistosome-infected mice that were simultaneously depleted of gut bacteria. After depletion there was significantly less inflammation in the intestine, which was accompanied by decreased intestinal granuloma development. In contrast, liver pathology remained unaltered. In addition, schistosome-specific immune responses were skewed and faecal egg excretion was diminished. This study demonstrates that host microbiota can act as a third partner in instigating helminth-specific immune responses.<\/jats:p>","DOI":"10.1111\/cei.12230","type":"journal-article","created":{"date-parts":[[2013,10,30]],"date-time":"2013-10-30T00:56:46Z","timestamp":1383094606000},"page":"246-257","source":"Crossref","is-referenced-by-count":66,"title":["Lack of host gut microbiota alters immune responses and intestinal granuloma formation during schistosomiasis"],"prefix":"10.1093","volume":"175","author":[{"given":"M","family":"Holzscheiter","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Immunologie und Hygiene (MIH), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L E","family":"Layland","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Immunologie und Hygiene (MIH), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"},{"name":"Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Clinic Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Loffredo-Verde","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Immunologie und Hygiene (MIH), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Mair","sequence":"additional","affiliation":[{"name":"II Medizinische Klinik und Poliklinik (Gastroenterologie), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Vogelmann","sequence":"additional","affiliation":[{"name":"II Medizinische Klinik und Poliklinik (Gastroenterologie), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Langer","sequence":"additional","affiliation":[{"name":"Institute of Pathology, Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Immunologie und Hygiene (MIH), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Prazeres da Costa","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Medizinische Mikrobiologie, Immunologie und Hygiene (MIH), Technische Universit\u00e4t M\u00fcnchen, M\u00fcnchen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,1,3]]},"reference":[{"key":"2021111804104872500_cei12230-bib-0001","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1038\/nri843","article-title":"The immunobiology of schistosomiasis","volume":"2","author":"Pearce","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"2021111804104872500_cei12230-bib-0002","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/sj.icb.7100014","article-title":"Immunopathology of schistosomiasis","volume":"85","author":"Wilson","year":"2007","journal-title":"Immunol Cell Biol"},{"key":"2021111804104872500_cei12230-bib-0003","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.trstmh.2009.08.006","article-title":"Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni","volume":"104","author":"Wilson","year":"2010","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2021111804104872500_cei12230-bib-0004","first-page":"250","article-title":"The generation of interferon-gamma-producing T lymphocytes in skin-draining lymph nodes, and their recruitment to the lungs, is associated with protective immunity to Schistosoma mansoni","volume":"75","author":"Mountford","year":"1992","journal-title":"Immunology"},{"key":"2021111804104872500_cei12230-bib-0005","doi-asserted-by":"crossref","first-page":"5200","DOI":"10.4049\/jimmunol.153.11.5200","article-title":"Elevated expression of Th1 cytokines and nitric oxide synthase in the lungs of vaccinated mice after challenge infection with Schistosoma mansoni","volume":"153","author":"Wynn","year":"1994","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0006","doi-asserted-by":"crossref","first-page":"3248","DOI":"10.1002\/eji.200526273","article-title":"Lack of antigen-specific Th1 response alters granuloma formation and composition in Schistosoma mansoni-infected MyD88\u2212\/\u2212 mice","volume":"35","author":"Layland","year":"2005","journal-title":"Eur J Immunol"},{"key":"2021111804104872500_cei12230-bib-0007","doi-asserted-by":"crossref","first-page":"2174","DOI":"10.1002\/eji.200737063","article-title":"Immunopathology in schistosomiasis is controlled by antigen-specific regulatory T cells primed in the presence of TLR2","volume":"37","author":"Layland","year":"2007","journal-title":"Eur J Immunol"},{"key":"2021111804104872500_cei12230-bib-0008","doi-asserted-by":"crossref","first-page":"713","DOI":"10.4049\/jimmunol.0901435","article-title":"Pronounced phenotype in activated regulatory T cells during a chronic helminth infection","volume":"184","author":"Layland","year":"2010","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0009","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.0105-2896.2004.00187.x","article-title":"Th2 polarisation during infection with the helminth parasite Schistosoma mansoni","volume":"201","author":"Pearce","year":"2004","journal-title":"Immunol Rev"},{"key":"2021111804104872500_cei12230-bib-0010","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1365-3024.2005.00765.x","article-title":"Priming of the immune response by schistosome eggs","volume":"27","author":"Pearce","year":"2005","journal-title":"Parasite Immunol"},{"key":"2021111804104872500_cei12230-bib-0011","doi-asserted-by":"crossref","first-page":"85","DOI":"10.4269\/ajtmh.1987.37.85","article-title":"Variation of hepatic fibrosis and granuloma size among mouse strains infected with Schistosoma mansoni","volume":"37","author":"Cheever","year":"1987","journal-title":"Am J Trop Med Hyg"},{"key":"2021111804104872500_cei12230-bib-0012","doi-asserted-by":"crossref","first-page":"13243","DOI":"10.1073\/pnas.231258498","article-title":"Th1-polarizing immunization with egg antigens correlates with severe exacerbation of immunopathology and death in schistosome infection","volume":"98","author":"Rutitzky","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021111804104872500_cei12230-bib-0013","doi-asserted-by":"crossref","first-page":"2585","DOI":"10.4049\/jimmunol.164.5.2585","article-title":"Schistosome infection of transgenic mice defines distinct and contrasting pathogenic roles for IL-4 and IL-13: IL-13 is a profibrotic agent","volume":"164","author":"Fallon","year":"2000","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0014","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.pt.2006.09.006","article-title":"Transmission control for schistosomiasis \u2013 why it matters now","volume":"22","author":"King","year":"2006","journal-title":"Trends Parasitol"},{"key":"2021111804104872500_cei12230-bib-0015","doi-asserted-by":"crossref","first-page":"7454","DOI":"10.4049\/jimmunol.173.12.7454","article-title":"Helminth antigens modulate TLR-initiated dendritic cell activation","volume":"173","author":"Kane","year":"2004","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0016","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1016\/j.molimm.2006.12.012","article-title":"Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation","volume":"44","author":"van Liempt","year":"2007","journal-title":"Mol Immunol"},{"key":"2021111804104872500_cei12230-bib-0017","doi-asserted-by":"crossref","first-page":"5999","DOI":"10.4049\/jimmunol.0900897","article-title":"Helminth antigens modulate immune responses in cells from multiple sclerosis patients through TLR2-dependent mechanisms","volume":"183","author":"Correale","year":"2009","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0018","doi-asserted-by":"crossref","first-page":"20459","DOI":"10.1073\/pnas.1010337107","article-title":"Schistosoma mansoni triggers Dectin-2 which activates the Nlrp3 inflammasome and alters adaptive immune responses","volume":"107","author":"Ritter","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021111804104872500_cei12230-bib-0019","doi-asserted-by":"crossref","first-page":"2026","DOI":"10.4049\/jimmunol.0901936","article-title":"Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditions","volume":"184","author":"Niess","year":"2010","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0020","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev.pathol.4.110807.092135","article-title":"Epithelial barriers in homeostasis and disease","volume":"5","author":"Marchiando","year":"2010","journal-title":"Annu Rev Pathol"},{"key":"2021111804104872500_cei12230-bib-0021","doi-asserted-by":"crossref","first-page":"8785","DOI":"10.4049\/jimmunol.177.12.8785","article-title":"Gram-negative bacteria aggravate murine small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii","volume":"177","author":"Heimesaat","year":"2006","journal-title":"J Immunol"},{"key":"2021111804104872500_cei12230-bib-0022","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1371\/journal.pone.0000662","article-title":"Shift towards pro-inflammatory intestinal bacteria aggravates acute murine colitis via Toll-like receptors 2 and 4","volume":"2","author":"Heimesaat","year":"2007","journal-title":"PLOS ONE"},{"key":"2021111804104872500_cei12230-bib-0023","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2004.07.002","article-title":"Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis","volume":"118","author":"Rakoff-Nahoum","year":"2004","journal-title":"Cell"},{"key":"2021111804104872500_cei12230-bib-0024","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1097\/00000478-199610000-00001","article-title":"Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994","volume":"10","author":"Dixon","year":"1996","journal-title":"Am J Surg Pathol"},{"key":"2021111804104872500_cei12230-bib-0025","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1111\/j.1440-1746.2008.05308.x","article-title":"Conditionally immortalized colonic epithelial cell line from a Ptk6 null mouse that polarizes and differentiates in vitro","volume":"23","author":"Whitehead","year":"2008","journal-title":"J Gastroenterol Hepatol"},{"key":"2021111804104872500_cei12230-bib-0026","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1590\/S0074-02762004000700009","article-title":"Alteration in the endogenous intestinal flora of Swiss Webster mice by experimental Angiostrongylus costaricensis infection","volume":"99","author":"Nobre","year":"2004","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"2021111804104872500_cei12230-bib-0027","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1128\/IAI.00919-08","article-title":"The Fasciola hepatica tegumental antigen suppresses dendritic cell maturation and function","volume":"6","author":"Hamilton","year":"2009","journal-title":"Infect Immun"},{"key":"2021111804104872500_cei12230-bib-0028","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.chom.2009.06.005","article-title":"Gut commensal bacteria direct a protective immune response against Toxoplasma gondii","volume":"6","author":"Benson","year":"2009","journal-title":"Cell Host Microbe"},{"key":"2021111804104872500_cei12230-bib-0029","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4269\/ajtmh.1997.56.515","article-title":"Studies on schistosomiasis in western Kenya: I. Evidence for immune-facilitated excretion of schistosome eggs from patients with Schistosoma mansoni and human immunodeficiency virus coinfections","volume":"56","author":"Karanja","year":"1997","journal-title":"Am J Trop Med Hyg"},{"key":"2021111804104872500_cei12230-bib-0030","first-page":"771","article-title":"Studies on the host\u2013parasite relationship in Schistosoma mansoni-infected mice: the immunological dependence of parasite egg excretion","volume":"35","author":"Doenhoff","year":"1978","journal-title":"Immunology"},{"key":"2021111804104872500_cei12230-bib-0031","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1038\/356604a0","article-title":"Tumour necrosis factor alpha restores granulomas and induces parasite egg-laying in schistosome-infected SCID mice","volume":"356","author":"Amiri","year":"1992","journal-title":"Nature"},{"key":"2021111804104872500_cei12230-bib-0032","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.1128\/IAI.67.5.2201-2208.1999","article-title":"Egg laying is delayed but worm fecundity is normal in SCID mice infected with Schistosoma japonicum and S. mansoni with or without recombinant tumor necrosis factor alpha treatment","volume":"67","author":"Cheever","year":"1999","journal-title":"Infect Immun"},{"key":"2021111804104872500_cei12230-bib-0033","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1128\/CMR.2.3.250","article-title":"Immunopathology of Schistosoma mansoni infection","volume":"2","author":"Boros","year":"1989","journal-title":"Clin Microbiol Rev"},{"key":"2021111804104872500_cei12230-bib-0034","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1590\/S0074-02762000000300010","article-title":"Significance of schistosomal granuloma modulation","volume":"95","author":"Silva","year":"2000","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"2021111804104872500_cei12230-bib-0035","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1016\/S1286-4579(00)01341-1","article-title":"Schistosoma mansoni egg-induced hepatic granulomas in mice deficient for the interferon-gamma receptor have altered populations of macrophages, lymphocytes and connective tissue cells","volume":"2","author":"Oliveira","year":"2000","journal-title":"Microbes Infect"},{"key":"2021111804104872500_cei12230-bib-0036","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1128\/iai.65.8.3457-3461.1997","article-title":"Mice lacking the gamma interferon receptor have an impaired granulomatous reaction to Schistosoma mansoni infection","volume":"65","author":"Rezende","year":"1997","journal-title":"Infect Immun"},{"key":"2021111804104872500_cei12230-bib-0037","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1159\/000231857","article-title":"Suppression of cell-mediated immunity by metronidazole","volume":"54","author":"Grove","year":"1977","journal-title":"Int Arch Allergy Appl Immunol"},{"key":"2021111804104872500_cei12230-bib-0038","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1590\/S0036-46651987000100006","article-title":"Schistosomiasis mansoni: evidence for a milder response in germfree mice","volume":"29","author":"Viera","year":"1987","journal-title":"Rev Inst Med Trop Sao Paulo"},{"key":"2021111804104872500_cei12230-bib-0039","first-page":"235","article-title":"Alterations in cell number, size and collagen content in livers of conventional and germfree mice bearing Schistosoma mansoni","volume":"181","author":"Vieira","year":"1985","journal-title":"Prog Clin Biol Res"},{"key":"2021111804104872500_cei12230-bib-0040","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1111\/j.0105-2896.2004.00176.x","article-title":"Immunopathogenesis of schistosomiasis","volume":"201","author":"Wynn","year":"2004","journal-title":"Immunol Rev"},{"key":"2021111804104872500_cei12230-bib-0041","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1006\/clin.1993.1095","article-title":"Lymphokine regulation of granuloma formation in murine Schistosomiasis mansoni","volume":"68","author":"Lukacs","year":"1993","journal-title":"Clin Immunol Immunopathol"},{"key":"2021111804104872500_cei12230-bib-0042","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/S0171-2985(11)80450-X","article-title":"The role of cytokines in the formation of the schistosome egg granuloma","volume":"191","author":"Boros","year":"1994","journal-title":"Immunobiology"},{"key":"2021111804104872500_cei12230-bib-0043","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1111\/j.1365-2249.1994.tb05503.x","article-title":"Cross-regulatory role of interferon-gamma (IFN-gamma), interleukin (IL)-4 and IL-10 in schistosome egg granuloma formation: in-vivo regulation of T helper activity and inflammation","volume":"98","author":"Chensue","year":"1994","journal-title":"Clin Exp Immunol"},{"key":"2021111804104872500_cei12230-bib-0044","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1126\/science.1187703","article-title":"Exploitation of the intestinal microflora by the parasitic nematode Trichuris muris","volume":"328","author":"Hayes","year":"2010","journal-title":"Science"}],"container-title":["Clinical and Experimental Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcei.12230","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/175\/2\/246\/41083235\/cei12230.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cei\/article-pdf\/175\/2\/246\/41083235\/cei12230.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T15:41:49Z","timestamp":1688571709000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cei\/article\/175\/2\/246\/6378146"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,3]]},"references-count":44,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2014,1,3]]},"published-print":{"date-parts":[[2014,1,3]]}},"URL":"https:\/\/doi.org\/10.1111\/cei.12230","relation":{},"ISSN":["0009-9104","1365-2249"],"issn-type":[{"value":"0009-9104","type":"print"},{"value":"1365-2249","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,2]]},"published":{"date-parts":[[2014,1,3]]}}}