{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T18:51:12Z","timestamp":1775501472967,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014069","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:00:00Z","timestamp":1775433600000}}],"reference-count":60,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Canada Graduate Research Scholarship"},{"name":"Emerging and Pandemic Infections Consortium"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007658","name":"Crohn's and Colitis Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007658","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The host response to commensal and pathogenic bacteria has been extensively characterized using human cancer cell line models but remains less defined in primary intestinal cellular systems. Recent evidence has demonstrated that mice lacking the Nod-like receptor (NLR) protein NLRC4 are susceptible to\n                    <jats:italic>Shigella flexneri<\/jats:italic>\n                    infection and thus represent a new model to study the mechanistic aspects of\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    -host interaction. Using ileal organoids from wild-type (WT) and\n                    <jats:italic>Nlrc4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice, we first confirmed that NLRC4 was required for the restriction of intracellular\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    growth. Surprisingly, NLRC4 further mediated the detection of bacteria-free\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    supernatants, suggesting that ileal organoids sample proteins from the type three secretion system (T3SS) of\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    to mediate a preemptive pyroptotic response to pathogens independently from invasion. Moreover, both invasive and non-invasive\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    were found within\n                    <jats:italic>Nlrc4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    ileal organoids, suggesting that murine intestinal epithelial cells (IECs) may be capable of bacterial uptake. Transcriptional analysis further revealed that infection of\n                    <jats:italic>Nlrc4<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    organoids with invasive or non-invasive\n                    <jats:italic>S. flexneri<\/jats:italic>\n                    resulted in the downregulation of inflammatory signaling. In addition, infection was associated with an enrichment for markers of the enteroendocrine cell (EEC) lineage, effects that required exposure to bacteria and were not recapitulated by bacteria-free supernatants. Together, our results reveal unexpected characteristics of host-bacterial interaction in primary murine IECs, which may shape the response to the microbiota and enteric pathogens at the intestinal mucosal surface.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014069","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T17:44:08Z","timestamp":1774287848000},"page":"e1014069","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Host response to bacteria induces a shift towards the enteroendocrine cell lineage in the murine enteroid model"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7451-6170","authenticated-orcid":true,"given":"Marry","family":"Nissan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrienne","family":"Ranger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin J.","family":"Meade","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Gillmore","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maija E.","family":"Lehn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liliane","family":"Cabral-Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Derek K. 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