{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T02:21:36Z","timestamp":1790389296221,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009987","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,11,5]],"date-time":"2021-11-05T00:00:00Z","timestamp":1636070400000}}],"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T00:00:00Z","timestamp":1634688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI116482"],"award-info":[{"award-number":["U19AI116482"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI116482"],"award-info":[{"award-number":["U19AI116482"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI116482"],"award-info":[{"award-number":["U19AI116482"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["U19AI116482"],"award-info":[{"award-number":["U19AI116482"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32AI007528"],"award-info":[{"award-number":["T32AI007528"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    represents over 2500 serovars associated with a wide-ranging spectrum of disease; from self-limiting gastroenteritis to invasive infections caused by non-typhoidal serovars (NTS) and typhoidal serovars, respectively. Host factors strongly influence infection outcome as malnourished or immunocompromised individuals can develop invasive infections from NTS, however, comparative analyses of serovar-specific host responses have been constrained by reliance on limited model systems. Here we used human intestinal organoids (HIOs), a three-dimensional \u201cgut-like\u201d\n                    <jats:italic>in vitro<\/jats:italic>\n                    system derived from human embryonic stem cells, to elucidate similarities and differences in host responses to NTS and typhoidal serovars. HIOs discriminated between the two most prevalent NTS,\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhimurium (STM) and\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Enteritidis (SE), and typhoidal serovar\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhi (ST) in epithelial cell invasion, replication and transcriptional responses. Pro-inflammatory signaling and cytokine output was reduced in ST-infected HIOs compared to NTS infections, consistent with early stages of NTS and typhoidal diseases. While we predicted that ST would induce a distinct transcriptional profile from the NTS strains, more nuanced expression profiles emerged. Notably, pathways involved in cell cycle, metabolism and mitochondrial functions were downregulated in STM-infected HIOs and upregulated in SE-infected HIOs. These results correlated with suppression of cellular proliferation and induction of host cell death in STM-infected HIOs and in contrast, elevated levels of reactive oxygen species production in SE-infected HIOs. Collectively, these results suggest that the HIO model is well suited to reveal host transcriptional programming specific to infection by individual\n                    <jats:italic>Salmonella<\/jats:italic>\n                    serovars, and that individual NTS may provoke unique host epithelial responses during intestinal stages of infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1009987","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T23:55:47Z","timestamp":1634774147000},"page":"e1009987","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Comparative transcriptional profiling of the early host response to infection by typhoidal and non-typhoidal Salmonella serovars in human intestinal organoids"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6492-2707","authenticated-orcid":true,"given":"Basel H.","family":"Abuaita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lisa E.","family":"Lawrence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0023-8129","authenticated-orcid":true,"given":"Ryan P.","family":"Berger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Hill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sha","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veda K.","family":"Yadagiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke","family":"Bons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-453X","authenticated-orcid":true,"given":"Courtney","family":"Fields","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5286-0924","authenticated-orcid":true,"given":"Christiane E.","family":"Wobus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason R.","family":"Spence","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3687-2364","authenticated-orcid":true,"given":"Vincent B.","family":"Young","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6014-4637","authenticated-orcid":true,"given":"Mary X.","family":"O\u2019Riordan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,10,20]]},"reference":[{"key":"ppat.1009987.ref001","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1086\/650733","article-title":"The global burden of nontyphoidal Salmonella gastroenteritis","volume":"50","author":"SE Majowicz","year":"2010","journal-title":"Clin Infect Dis"},{"key":"ppat.1009987.ref002","first-page":"346","article-title":"The global burden of typhoid fever","volume":"82","author":"JA Crump","year":"2004","journal-title":"Bull World Health Organ"},{"key":"ppat.1009987.ref003","article-title":"Salmonella serovars and their host specificity.","volume":"1","author":"V Singh","year":"2013","journal-title":"J Vet Sci Anim Husb."},{"key":"ppat.1009987.ref004","doi-asserted-by":"crossref","first-page":"391","DOI":"10.3389\/fmicb.2014.00391","article-title":"Same species, different diseases: how and why typhoidal and non-typhoidal Salmonella enterica serovars differ.","volume":"5","author":"O Gal-Mor","year":"2014","journal-title":"Front Microbiol"},{"key":"ppat.1009987.ref005","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1101\/gr.077404.108","article-title":"Comparative genome analysis of Salmonella Enteritidis PT4 and Salmonella Gallinarum 287\/91 provides insights into evolutionary and host adaptation pathways","volume":"18","author":"NR Thomson","year":"2008","journal-title":"Genome Res"},{"key":"ppat.1009987.ref006","first-page":"e00929","article-title":"Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut","volume":"5","author":"S-P 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