{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:22:57Z","timestamp":1784694177885,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,4,19]],"date-time":"2023-04-19T00:00:00Z","timestamp":1681862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1139371"],"award-info":[{"award-number":["APP1139371"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["CA210128"],"award-info":[{"award-number":["CA210128"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2023,5]]},"abstract":"Abstract<\/jats:title>Helicobacter pylori<\/jats:italic> (H.\u2009pylori<\/jats:italic>) infection can trigger chronic gastric inflammation perpetuated by overactivation of the innate immune system, leading to a cascade of precancerous lesions culminating in gastric cancer. However, key regulators of innate immunity that promote H.\u2009pylori<\/jats:italic>\u2013induced gastric pathology remain ill\u2010defined. The innate immune cytosolic DNA sensor absent in melanoma 2 (AIM2) contributes to the pathogenesis of numerous autoimmune and chronic inflammatory diseases, as well as cancers including gastric cancer. We therefore investigated whether AIM2 contributed to the pathogenesis of Helicobacter<\/jats:italic>\u2010induced gastric disease. Here, we reveal that AIM2 messenger RNA and protein expression levels are elevated in H.\u2009pylori<\/jats:italic>\u2013positive versus H.\u2009pylori<\/jats:italic>\u2013negative human gastric biopsies. Similarly, chronic Helicobacter felis<\/jats:italic> infection in wild\u2010type mice augmented Aim2<\/jats:italic> gene expression levels compared with uninfected controls. Notably, gastric inflammation and hyperplasia were less severe in H.\u2009felis<\/jats:italic>\u2013infected Aim2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> versus<\/jats:italic> wild\u2010type mice, evidenced by reductions in gastric immune cell infiltrates, mucosal thickness and proinflammatory cytokine and chemokine release. In addition, H.\u2009felis<\/jats:italic>\u2013driven proliferation and apoptosis in both gastric epithelial and immune cells were largely attenuated in Aim2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> stomachs. These observations in Aim2<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> mouse stomachs correlated with decreased levels of inflammasome activity (caspase\u20101 cleavage) and the mature inflammasome effector cytokine, interleukin\u20101\u03b2. Taken together, this work uncovers a pathogenic role for the AIM2 inflammasome in Helicobacter<\/jats:italic>\u2010induced gastric disease, and furthers our understanding of the host immune response to a common pathogen and the complex and varying roles of AIM2 at different stages of cancerous and precancerous gastric disease.<\/jats:p>","DOI":"10.1111\/imcb.12641","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T06:47:30Z","timestamp":1679899650000},"page":"444-457","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The cytosolic DNA sensor AIM2 promotes Helicobacter<\/i>\u2010induced gastric pathology via<\/i> the inflammasome"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9797-7800","authenticated-orcid":false,"given":"Ruby E","family":"Dawson","sequence":"first","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Deswaerte","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison C","family":"West","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekimei","family":"Sun","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgie","family":"Wray\u2010McCann","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thaleia","family":"Livis","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beena","family":"Kumar","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology Monash Health Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliana","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Pathology and Immunology Department CMU\/University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Gabay","sequence":"additional","affiliation":[{"name":"Pathology and Immunology Department CMU\/University of Geneva Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6817-6211","authenticated-orcid":false,"given":"Richard L","family":"Ferrero","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"},{"name":"Department of Microbiology, Biomedicine Discovery Institute Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan J","family":"Jenkins","sequence":"additional","affiliation":[{"name":"Centre for Innate Immunity and Infectious Diseases Hudson Institute of Medical Research Clayton VIC Australia"},{"name":"Department of Molecular and Translational Science, Faculty of Medicine, Nursing and Health Sciences Monash University Clayton VIC Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30111"},{"key":"e_1_2_10_3_1","first-page":"59","article-title":"Helicobacter pylori infection and gastric adenocarcinoma","volume":"7","author":"Correa P","year":"2011","journal-title":"US Gastroenterol Hepatol Rev"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-85563-1.00004-6"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.5506"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00449-x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro3016"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni1131"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftu024"},{"key":"e_1_2_10_10_1","first-page":"336","article-title":"Pattern\u2010recognition receptors and gastric cancer","volume":"5","author":"Castano\u2010Rodriguez N","year":"2014","journal-title":"Front Immunol"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400362"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900351"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb0391"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-022-00462-5"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1381612821666150514104411"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1000864"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.08.080"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305536200"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2022.06.002"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.08.010"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0900664"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2008.952366"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2008.10.011"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.07.034"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-17-1887"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.001"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201848070"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/cmi.2016.35"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323916"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.94035"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-005-2_20"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2020.01.021"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2022.2105102"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39858"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-018-0639-3"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3908"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.10.040"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-011811-120905"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-005-2_12"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2015.142"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07725"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1864"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01121"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209171109"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20100050"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016814108"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2000915118"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2933"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11040504"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.01.006"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(90)91156-Z"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1099\/00207713-41-1-31"}],"container-title":["Immunology & Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.12641","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/imcb.12641","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T20:35:21Z","timestamp":1692650121000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/imcb.12641"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,19]]},"references-count":51,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5]]}},"alternative-id":["10.1111\/imcb.12641"],"URL":"https:\/\/doi.org\/10.1111\/imcb.12641","archive":["Portico"],"relation":{},"ISSN":["0818-9641","1440-1711"],"issn-type":[{"value":"0818-9641","type":"print"},{"value":"1440-1711","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,19]]},"assertion":[{"value":"2022-10-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}