{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T18:13:14Z","timestamp":1779300794297,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014232","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000}}],"reference-count":64,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32302879"],"award-info":[{"award-number":["32302879"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32202889"],"award-info":[{"award-number":["32202889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302566"],"award-info":[{"award-number":["82302566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Science and Technology Development Plan of Jilin Province","award":["20260102224JC"],"award-info":[{"award-number":["20260102224JC"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Leptospirosis, caused by pathogenic\n                    <jats:italic>Leptospira<\/jats:italic>\n                    species, is a globally significant zoonotic disease with high morbidity and mortality. However, the organs or cells mainly involved in capturing circulating leptospires and the related mechanisms remain poorly understood. In this study, we firstly proved that the liver was the primary organ that captured leptospires during the very early intravascular phase of infection in mice. Then, we used unbiased flow sorting of leptospires-positive cells and intravital microscopy of mice infected with leptospires, and found that liver macrophages were the main leptospires-capturing immune cells. The depletion of liver macrophages abolished the ability of liver to capture leptospires and prompted leptospiral spread in other organs. The C-type lectin receptor signaling pathway and\n                    <jats:italic>Clec4d<\/jats:italic>\n                    were identified as the differential pathways and gene through RNA-seq analysis, respectively. The ectopic expression of Clec4d in HEK-293T cells or treatment with a Clec4d inhibitor, mannan proved that Clec4d functioned as a capture receptor of leptospires. Mechanistically, the transcription factor CCAAT\/enhancer-binding protein beta (C\/EBP\u03b2) was activated and directly bound to the promoter of\n                    <jats:italic>Clec4d<\/jats:italic>\n                    to promote the expression of Clec4d in liver macrophages, thereby enhancing leptospiral capture. Mice treated with C\/EBP\u03b2 inhibitor showed a significant inhibition of liver macrophages in capturing leptospires and increased leptospiral load in other organs. Our findings identify a novel mechanism by which the liver macrophages restrict leptospiral dissemination through C\/EBP\u03b2-Clec4d axis, and suggest a therapeutic strategy to prevent leptospiral dissemination through enhancing liver macrophages functions.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014232","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T17:49:59Z","timestamp":1778694599000},"page":"e1014232","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leptospiral dissemination is restrained by liver macrophages through Clec4d-driven capture via C\/EBP\u03b2 activation"],"prefix":"10.1371","volume":"22","author":[{"given":"Xi","family":"Chen","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiuxi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haixin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xufeng","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9533-7516","authenticated-orcid":true,"given":"Yongguo","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"issue":"1","key":"ppat.1014232.ref001","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41572-025-00614-5","article-title":"Leptospirosis","volume":"11","author":"S 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