{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:30:52Z","timestamp":1786559452065,"version":"build-2736575974"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014152","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015691","name":"Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI042347"],"award-info":[{"award-number":["R01AI042347"]}],"id":[{"id":"10.13039\/100015691","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 liver receives microbe and host signals from the intestine via the portal vein, thereby connecting the gut to systemic physiology. Homeostatic control of the timing of systemic responses is critical to prevent the expansion and dissemination of gut microbes and to mitigate untoward effects from prolonged systemic inflammation, however these mechanisms remain enigmatic. Here, to determine the role of the liver in coordinating systemic immune responses to enteric infection, matched measurements of global gene expression profiles were collected from the murine liver and intestinal epithelium throughout the course of enteric infection and clearance of\n                    <jats:italic>Citrobacter rodentium<\/jats:italic>\n                    , a mouse model of infectious colitis. These data revealed metabolic suppression in the liver during the peak of infection and a long-lived immune signaling pattern in the colon associated with CD4 and CD8 T cell infiltration that persisted beyond the clearance of infection. Furthermore, an early inflammatory signal was detected in the liver that resolved before the peak of disease and pathogen colonization. This self-limited, early signal depended on the pathogen\u2019s virulence program and correlated with the timing of a corresponding systemic response, including circulating TNF-\u03b1 and IL-6, key mediators of acute-phase proteins. These results uncover the temporal pattern of hepatic changes in response to the course of intestinal infection and provide correlative evidence that an early pulse of gene expression in the liver coordinates and limits the duration of the systemic acute-phase protein response.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014152","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:39:09Z","timestamp":1785951549000},"page":"e1014152","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transcriptomic timeseries links hepatic gene expression to an early and self-limited systemic response to enteric infection"],"prefix":"10.1371","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6890-3933","authenticated-orcid":true,"given":"Yuko","family":"Hasegawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akina","family":"Osaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5352-8595","authenticated-orcid":true,"given":"Masataka","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9072-3821","authenticated-orcid":true,"given":"Ting","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian W.","family":"Campbell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1843-7000","authenticated-orcid":true,"given":"Matthew K.","family":"Waldor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"5","key":"ppat.1014152.ref001","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMra2206346","article-title":"Humoral innate immunity and acute-phase proteins","volume":"388","author":"A Mantovani","year":"2023","journal-title":"N Engl J Med"},{"issue":"10","key":"ppat.1014152.ref002","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1038\/s41591-020-1051-9","article-title":"An inflammatory cytokine signature predicts COVID-19 severity and survival","volume":"26","author":"DM Del Valle","year":"2020","journal-title":"Nat 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Jiang","year":"2020","journal-title":"Physiology"},{"key":"ppat.1014152.ref012","doi-asserted-by":"crossref","first-page":"101859","DOI":"10.1016\/j.smim.2023.101859","article-title":"Gut-liver axis: pathophysiological concepts and medical perspective in chronic liver diseases","volume":"71","author":"SG Rodrigues","year":"2024","journal-title":"Semin Immunol"},{"issue":"11","key":"ppat.1014152.ref013","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41579-023-00904-3","article-title":"The gut-liver axis and gut microbiota in health and liver disease","volume":"21","author":"CL Hsu","year":"2023","journal-title":"Nat Rev Microbiol"},{"key":"ppat.1014152.ref014","doi-asserted-by":"crossref","first-page":"1667180","DOI":"10.3389\/fimmu.2026.1667180","article-title":"Pathogenesis and intervention strategies for metabolic dysfunction-associated fatty liver disease from the perspective of the gut-microbiota-liver axis","volume":"17","author":"J Liao","year":"2026","journal-title":"Front Immunol"},{"issue":"7","key":"ppat.1014152.ref015","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1084\/jem.20091474","article-title":"Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function","volume":"207","author":"LE Sander","year":"2010","journal-title":"J Exp Med"},{"issue":"12","key":"ppat.1014152.ref016","doi-asserted-by":"crossref","first-page":"3376","DOI":"10.1038\/s41564-024-01862-z","article-title":"Enteric bacterial infection stimulates remodelling of bile metabolites to promote intestinal homeostasis","volume":"9","author":"T Zhang","year":"2024","journal-title":"Nat Microbiol"},{"key":"ppat.1014152.ref017","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1194\/jlr.R900010-JLR200","article-title":"Bile acids: regulation of synthesis","volume":"50","author":"JYL Chiang","year":"2009","journal-title":"J Lipid 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Berger","year":"2018","journal-title":"PLoS Pathog"},{"issue":"6","key":"ppat.1014152.ref037","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.1128\/IAI.01343-09","article-title":"Gamma interferon produced by antigen-specific CD4+ T cells regulates the mucosal immune responses to Citrobacter rodentium infection","volume":"78","author":"H Shiomi","year":"2010","journal-title":"Infect Immun"},{"issue":"7","key":"ppat.1014152.ref038","doi-asserted-by":"crossref","DOI":"10.1128\/IAI.00295-19","article-title":"Citrobacter rodentium induces tissue-resident memory CD4+ T cells","volume":"87","author":"S Bishu","year":"2019","journal-title":"Infect Immun"},{"issue":"11","key":"ppat.1014152.ref039","doi-asserted-by":"crossref","first-page":"4654","DOI":"10.1128\/iai.61.11.4654-4661.1993","article-title":"The eae gene of Citrobacter freundii biotype 4280 is necessary for colonization in transmissible murine colonic hyperplasia","volume":"61","author":"DB Schauer","year":"1993","journal-title":"Infect Immun"},{"issue":"9","key":"ppat.1014152.ref040","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1515\/hsz-2021-0209","article-title":"Acute-phase protein synthesis: a key feature of innate immune functions of the liver","volume":"402","author":"C Ehlting","year":"2021","journal-title":"Biol Chem"},{"issue":"2","key":"ppat.1014152.ref041","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.cell.2015.08.058","article-title":"Th17 cell induction by adhesion of microbes to intestinal epithelial cells","volume":"163","author":"K Atarashi","year":"2015","journal-title":"Cell"},{"issue":"6","key":"ppat.1014152.ref042","doi-asserted-by":"crossref","first-page":"3031","DOI":"10.1128\/IAI.67.6.3031-3039.1999","article-title":"Citrobacter rodentium infection in mice elicits a mucosal Th1 cytokine response and lesions similar to those in murine inflammatory bowel disease","volume":"67","author":"LM 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