{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T16:43:04Z","timestamp":1793032984987,"version":"4.5.0"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,9,11]],"date-time":"2017-09-11T00:00:00Z","timestamp":1505088000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["BSCGIO_157841\/1"],"award-info":[{"award-number":["BSCGIO_157841\/1"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI039657 and CA116087"],"award-info":[{"award-number":["AI039657 and CA116087"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Food allergy is an increasingly common health problem in Western populations. Epidemiological studies have suggested both positive and negative associations between food allergy and infection with the gastric bacterium <jats:italic>Helicobacter pylori<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>The objective of this work was to investigate whether experimental infection with <jats:italic>H. pylori<\/jats:italic>, or prophylactic treatment with <jats:italic>H. pylori<\/jats:italic>\u2010derived immunomodulatory molecules, affects the onset and severity of food allergy, either positively or negatively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We infected neonatal C57<jats:styled-content style=\"fixed-case\">BL<\/jats:styled-content>\/6 or C3H mice with <jats:italic>H. pylori<\/jats:italic> or treated animals with <jats:italic>H. pylori<\/jats:italic> components (bacterial lysate or the immunomodulator VacA) and subsequently subjected them to four different protocols for food allergy induction, using either ovalbumin or peanut extract as allergens for sensitization and challenge. Readouts included anaphylaxis scoring, quantification of allergen\u2010specific serum IgE and IgG1 and of the mast cell protease <jats:styled-content style=\"fixed-case\">MCPT<\/jats:styled-content>1, as well as splenic T\u2010helper\u20102 cell\u2010derived cytokine production. Mesenteric lymph node <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> regulatory T cells were subjected to flow cytometric quantification and sorting followed by <jats:styled-content style=\"fixed-case\">qRT<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">PCR<\/jats:styled-content>, and to <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> methylation analyses of the Treg\u2010specific demethylated region (<jats:styled-content style=\"fixed-case\">TSDR<\/jats:styled-content>) within the <jats:italic><jats:styled-content style=\"fixed-case\">FOXP<\/jats:styled-content>3<\/jats:italic> locus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice that had been infected with <jats:italic>H. pylori<\/jats:italic> or treated with <jats:italic>H. pylori<\/jats:italic>\u2010derived immunomodulators showed reduced anaphylaxis upon allergen sensitization and challenge, irrespective of the allergen used. Most of the immunologic assays confirmed a protective effect of <jats:italic>H. pylori<\/jats:italic>. <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>4<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> T cells were more abundant in protected mice and exhibited a stable Treg phenotype characterized by <jats:italic><jats:styled-content style=\"fixed-case\">FOXP<\/jats:styled-content>3 <\/jats:italic><jats:styled-content style=\"fixed-case\">TSDR<\/jats:styled-content> demethylation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Clinical Relevance<\/jats:title><jats:p><jats:italic>Helicobacter pylori<\/jats:italic> confers protection against the anaphylaxis associated with ovalbumin and peanut allergy and affects the epigenome of T cells, thereby promoting stable Treg differentiation and functionality. Prophylactic treatment with <jats:italic>H. pylori<\/jats:italic>\u2010derived immunomodulators appears to be a promising strategy for food allergy prevention.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.12996","type":"journal-article","created":{"date-parts":[[2017,8,12]],"date-time":"2017-08-12T13:02:39Z","timestamp":1502542959000},"page":"1331-1341","source":"Crossref","is-referenced-by-count":34,"title":["<i>Helicobacter pylori<\/i> and its secreted immunomodulator VacA protect against anaphylaxis in experimental models of food allergy"],"prefix":"10.1111","volume":"47","author":[{"given":"A.","family":"Kyburz","sequence":"first","affiliation":[{"name":"Institute of Molecular Cancer Research University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Urban","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Altobelli","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Floess","sequence":"additional","affiliation":[{"name":"Department Experimental Immunology Helmholtz Center for Infection Research Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Huehn","sequence":"additional","affiliation":[{"name":"Department Experimental Immunology Helmholtz Center for Infection Research Braunschweig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. L.","family":"Cover","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center and Veterans Affairs Tennessee Valley Healthcare System Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1368-8276","authenticated-orcid":false,"given":"A.","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Molecular Cancer Research University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-1210"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.11.020"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.299.6710.1259"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2245"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199110173251603"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.08.033"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1159\/000443357"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2015.1105427"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hel.12012"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1086\/590158"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21116"},{"key":"e_1_2_8_13_1","first-page":"CR452","article-title":"Helicobacter pylori as a protective factor against food allergy","volume":"14","author":"Konturek PC","year":"2008","journal-title":"Med Sci Monit"},{"key":"e_1_2_8_14_1","first-page":"368","article-title":"Food Allergy and Helicobacter pylori Infection: a systematic review","volume":"7","author":"Ma ZF","year":"2016","journal-title":"Front Microbiol"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365529850172467"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-3038.2000.00028.x"},{"key":"e_1_2_8_17_1","first-page":"827","article-title":"CagA\u2010positive Helicobacter pylori infection may increase the risk of food allergy development","volume":"50","author":"Figura N","year":"1999","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-200502000-00018"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI79337"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45041"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI61029"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2010.06.047"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1410579111"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.74"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2006.01012.x"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1203473"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200838105"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2007.133462"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004060"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.142"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211248110"}],"container-title":["Clinical &amp; Experimental Allergy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcea.12996","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cea.12996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T11:09:06Z","timestamp":1696331346000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cea.12996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,11]]},"references-count":30,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017,10]]}},"alternative-id":["10.1111\/cea.12996"],"URL":"https:\/\/doi.org\/10.1111\/cea.12996","archive":["Portico"],"relation":{},"ISSN":["0954-7894","1365-2222"],"issn-type":[{"value":"0954-7894","type":"print"},{"value":"1365-2222","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,11]]}}}