{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T23:52:09Z","timestamp":1773877929645,"version":"3.50.1"},"reference-count":22,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Innate Immun"],"abstract":"<jats:p>Introduction: Interleukin (IL)-6 has an important role in limiting urinary tract infection (UTI). Mice lacking IL-6 are more susceptible to uropathogenic Escherichia coli (UPEC), including increased formation of intracellular bacterial communities (IBCs). How IL-6 promotes UPEC clearance is unknown. We hypothesize IL-6 reduces UTI susceptibility by limiting IBC formation through an early mechanism of infection. Methods: Female mice were treated with vehicle or neutralizing antibodies to inhibit IL-6 or the IL-6 receptor (IL-6R) prior to transurethral UPEC infection. In rescue experiments, murine recombinant (r)IL-6 was administered to IL-6 knockout (KO) mice. Bladder IBCs, urinary and bladder bacterial burden, and UPEC expulsion were quantified. For clinical translation, human urothelial cells were pretreated with human rIL-6 and infected with UPEC. Bacterial attachment, invasion, and expulsion were quantified. Results: Neutralization of IL-6 or IL-6R increased bladder IBC counts compared to isotype controls. Similarly, while IL-6 KO mice exhibited higher IBC counts than wild-type controls, this phenotype was reversed by rIL-6 administration. Gentamicin protection assays confirmed increased intracellular UPEC burden and reduced bacterial expulsion in IL-6 KO bladders. rIL-6 treatment enhanced UPEC expulsion in human urothelial cells without impacting bacterial attachment or invasion. Conclusion: IL-6 facilitates UPEC expulsion, limiting intracellular UPEC early in infection and thus the initial formation of IBCs. Since IBC formation is a bottleneck in UPEC survival during UTI, these findings identify a mechanism whereby IL-6 reduces early UPEC urothelial infectivity.<\/jats:p>","DOI":"10.1159\/000550787","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T17:00:59Z","timestamp":1769792459000},"page":"120-125","source":"Crossref","is-referenced-by-count":0,"title":["Interleukin-6 Limits Host Susceptibility to Urinary Tract Infection by Promoting Urothelial Expulsion of Intracellular Bacteria"],"prefix":"10.1159","volume":"18","author":[{"given":"Sudipti","family":"Gupta","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shradha","family":"Rajak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Cortado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2750-4415","authenticated-orcid":false,"given":"Brian","family":"Becknell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John David","family":"Spencer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3396-4215","authenticated-orcid":false,"given":"Christina Barbara","family":"Ching","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2026,1,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308125100"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00355-06"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00339.x"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110698"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00691.x"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2017.12.006"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1128\/iai.58.5.1281-1289.1990"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.268"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00471.2016"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05339-11"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2017.08.002"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00592.2020"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2018090929"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114007"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2400666121"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1038\/nm1572"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.05.009"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900527106"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00069-08"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.7.3999-4006.2005"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-019-04269-9"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/s41585-024-00877-9"}],"container-title":["Journal of Innate Immunity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000550787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:00:54Z","timestamp":1773853254000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000550787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,30]]},"references-count":22,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000550787","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.31208566","asserted-by":"subject"}]},"ISSN":["1662-811X","1662-8128"],"issn-type":[{"value":"1662-811X","type":"print"},{"value":"1662-8128","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,30]]}}}