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In the UK, over 75% of chicken products are\n              <jats:italic>Campylobacter<\/jats:italic>\n              -positive at retail, but the knowledge of the mechanisms responsible for extraintestinal spread into edible tissues remains incomplete. This work aimed to establish if two chicken-associated lineages of\n              <jats:italic>Campylobacter jejuni<\/jats:italic>\n              , ST353 and ST464, have the potential for extraintestinal spread. Large- and small-scale chicken colonization trials investigated the infection biology of\n              <jats:italic>C. jejuni<\/jats:italic>\n              ST353 (three strains) and ST464 (four strains). Both lineages strongly colonized the ileum and ceca and were detected in liver and spleen.\n              <jats:italic>C. jejuni<\/jats:italic>\n              ST353 and ST464 spleen load were significantly increased compared to\n              <jats:italic>C. jejuni<\/jats:italic>\n              M1 controls. Immune responses in cecal tonsils exhibited early induction of IFN-\u03b3 and suppressed TGF\u03b2 at 7 days post-infection with\n              <jats:italic>C. jejuni<\/jats:italic>\n              ST464. Histochemistry of gut tissue demonstrated significant decreases in intestinal crypt depth in ileal tissue with increasing severity relative to\n              <jats:italic>Campylobacter<\/jats:italic>\n              lineage, M1 &lt;ST353&lt;ST464. Pairwise correlation analysis confirmed strong interdependencies between \u201ccecal\n              <jats:italic>Campylobacter<\/jats:italic>\n              load,\u201d \u201cCXCLi1,\u201d \u201cCXCLi2,\u201d and \u201csplenic\n              <jats:italic>Campylobacter<\/jats:italic>\n              load.\u201d Furthermore, linear discriminant analysis confirmed that cecal tonsil-derived IFN\u03b3, TGF\u03b2, and CXCLi1 could predict splenic invasion at 71% accuracy. This work demonstrates that two chicken specialist\n              <jats:italic>C. jejuni<\/jats:italic>\n              lineages, ST353 and ST464, cause extraintestinal spread to liver and spleen and modeling suggests distinct routes from ileum and cecum, respectively. Recognition of these two routes of\n              <jats:italic>Campylobacter<\/jats:italic>\n              extraintestinal spread (ileal\/liver and cecal\/spleen) provides a better understanding of this food-derived pathogen for academia and the industry.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                The UK is self-sufficient in chicken meat production, which remains a cheap and healthy source of dietary protein. However,\n                <jats:italic>Campylobacter<\/jats:italic>\n                species are present in 75% of raw chicken products at retail sales, resulting in increased human gut infections. Currently, it is not clear which members of the\n                <jats:italic>Campylobacter jejuni<\/jats:italic>\n                species can leave the digestive tract and reach edible tissues. Using industry-relevant conditions, two\n                <jats:italic>C. jejuni<\/jats:italic>\n                lineages (ST353 and ST464) isolated from chicken gut and liver were shown to cause infections outside the gut. The underlying mechanisms involve inducing inflammation and gut damage to structures required for cell renewal (crypts) of the intestine. Modeling this data leads to our proposal that\n                <jats:italic>C. jejuni<\/jats:italic>\n                uses two invasion pathways; one where spread is from ileum to liver and the other between ceca and spleen. Knowledge of these two routes of extraintestinal spread will help the industry develop control measures to improve food biosecurity in poultry.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/aem.01614-24","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T13:05:19Z","timestamp":1739883919000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["<i>Campylobacter jejuni<\/i>\n            ST353 and ST464 cause localized gut inflammation, crypt damage, and extraintestinal spread during large- and small-scale infection in broiler chickens"],"prefix":"10.1128","volume":"91","author":[{"given":"Heather M.","family":"Chick","sequence":"first","affiliation":[{"name":"Microbiology and Infectious Disease, Institute of Life Science, Swansea University Medical School","place":["Swansea, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"Williams","sequence":"additional","affiliation":[{"name":"Microbiology and Infectious Disease, Institute of Life Science, Swansea University Medical School","place":["Swansea, United Kingdom"]},{"name":"Department of Animal and Agriculture, Hartpury University","place":["Gloucester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick","family":"Sparks","sequence":"additional","affiliation":[{"name":"Scotland\u2019s Rural College (SRUC) Barony Campus","place":["Dumfries, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farina","family":"Khattak","sequence":"additional","affiliation":[{"name":"Monogastric Science Research Center, Scotland\u2019s Rural College (SRUC)","place":["Edinburgh, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Vermeij","sequence":"additional","affiliation":[{"name":"MSD Animal Health","place":["Boxmeer, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge","family":"Frantzen","sequence":"additional","affiliation":[{"name":"MSD Animal Health","place":["Boxmeer, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandy","family":"Peeters","sequence":"additional","affiliation":[{"name":"MSD Animal Health","place":["Boxmeer, the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jetta J. 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