{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:06:33Z","timestamp":1790687193207,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2020,4,14]],"date-time":"2020-04-14T00:00:00Z","timestamp":1586822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["12\/10395-0"],"award-info":[{"award-number":["12\/10395-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pattern recognition receptors (PRRs), such as Nod2, Nlrp3, Tlr2, Trl4, and Tlr9, are directly involved in type 1 diabetes (T1D) susceptibility. However, the role of the cytosolic DNA sensor, AIM2, in T1D pathogenesis is still unknown. Here, we demonstrate that C57BL\/6 mice lacking AIM2 (AIM2\u2212\/\u2212) are prone to streptozotocin (STZ)-induced T1D, compared to WT C57BL\/6 mice. The AIM2\u2212\/\u2212 mice phenotype is associated with a greater proinflammatory response in pancreatic tissues, alterations in gut microbiota and bacterial translocation to pancreatic lymph nodes (PLNs). These alterations are related to an increased intestinal permeability mediated by tight-junction disruption. Notably, AIM2\u2212\/\u2212 mice treated with broad-spectrum antibiotics (ABX) are protected from STZ-induced T1D and display a lower pancreatic proinflammatory response. Mechanistically, the AIM2 inflammasome is activated in vivo, leading to an IL-18 release in the ileum at 15 days after an STZ injection. IL-18 favors RegIII\u03b3 production, thus mitigating gut microbiota alterations and reinforcing the intestinal barrier function. Together, our findings show a regulatory role of AIM2, mediated by IL-18, in shaping gut microbiota and reducing bacterial translocation and proinflammatory response against insulin-producing \u03b2 cells, which ultimately results in protection against T1D onset in an STZ-induced diabetes model.<\/jats:p>","DOI":"10.3390\/cells9040959","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T04:01:46Z","timestamp":1586923306000},"page":"959","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The DNA Sensor AIM2 Protects against Streptozotocin-Induced Type 1 Diabetes by Regulating Intestinal Homeostasis via the IL-18 Pathway"],"prefix":"10.3390","volume":"9","author":[{"given":"Jefferson Ant\u00f4nio","family":"Leite","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, USP\u2014Avenida Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"},{"name":"Institute of Biomedical Science IV\u2014University of S\u00e3o Paulo (USP), S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3450-4816","authenticated-orcid":false,"given":"Gabriela","family":"Pessenda","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, USP\u2014Avenida Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9238-5793","authenticated-orcid":false,"given":"Isabel C.","family":"Guerra-Gomes","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, USP\u2014Avenida Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alynne Karen Mendon\u00e7a","family":"de Santana","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, USP\u2014Avenida Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Andr\u00e9 Pereira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederico","family":"Ribeiro Campos Costa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, USP\u2014Avenida Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone G.","family":"Ramos","sequence":"additional","affiliation":[{"name":"Department of Pathology and Legal Medicine, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Sim\u00f5es Zamboni","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Ribeir\u00e3o Preto Medical School, University of S\u00e3o Paulo (USP), Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria","family":"Caetano Faria","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Institute of Biological Science\u2014Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais 31270-901, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3661-2124","authenticated-orcid":false,"given":"Danilo","family":"Candido de Almeida","sequence":"additional","affiliation":[{"name":"Department of Immunology\u2014Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels","family":"Olsen Saraiva C\u00e2mara","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Immunology, Ribeir\u00e3o Preto Medical School, USP\u2014Avenida Bandeirantes 3900, Monte Alegre, Ribeir\u00e3o Preto, S\u00e3o Paulo 14049-900, Brazil"},{"name":"Institute of Biomedical Science IV\u2014University of S\u00e3o Paulo (USP), S\u00e3o Paulo, S\u00e3o Paulo 14049-900, Brazil"},{"name":"Department of Immunology\u2014Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo, S\u00e3o Paulo 04021-001, 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