{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:36:25Z","timestamp":1790858185167,"version":"4.1.0"},"reference-count":122,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    Urinary tract infections (UTIs) pose a significant global health burden, characterized by a spectrum of clinical outcomes shaped by intricate epithelial-immune interactions. Uropathogenic\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    (UPEC) is the predominant etiological agent, accounting for the majority of cystitis cases. Upon breaching urothelial barriers, UPEC triggers a robust innate immune response involving cytokine secretion, antimicrobial peptide production, and recruitment of neutrophils and other immune cells. This review synthesizes current understanding of the dynamic crosstalk between urothelial and immune cells\u2014highlighting mechanisms of bacterial recognition, phagocytosis, inflammatory mediation, and tissue repair\u2014while addressing the limited adaptive immunity, which underlies the high recurrence rates. Elucidating these interactions provides a framework for developing targeted immunomodulatory therapies against UTIs.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1792758","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T06:48:36Z","timestamp":1773902916000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Decoding epithelial-immune cell crosstalk in uropathogenic Escherichia coli urinary tract infections"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhenyu","family":"Jin","sequence":"first","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenyu","family":"Zhou","sequence":"additional","affiliation":[{"name":"Medical Research Center, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengguo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"S51","DOI":"10.1086\/318853","article-title":"Type 1 fimbriated Escherichia coli-mast cell interactions in cystitis","volume":"183","author":"Abraham","year":"2001","journal-title":"J. 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Immunol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1038\/nm1572","article-title":"Cyclic amp\u2013regulated exocytosis of Escherichia coli from infected bladder epithelial cells","volume":"13","author":"Bishop","year":"2007","journal-title":"Nat. Med."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41577-024-01079-5","article-title":"Striking a balance: new perspectives on homeostatic dendritic cell maturation","volume":"25","author":"Bosteels","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/s41385-020-0269-7","article-title":"Spatial proteomics revealed a Cx3cl1-dependent crosstalk between the urothelium and relocated macrophages through Il-6 during an acute bacterial infection in the urinary bladder","volume":"13","author":"Bottek","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1146\/annurev-immunol-101220-032117","article-title":"Tissue immunity in the bladder","volume":"40","author":"Bowyer","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"11015","DOI":"10.1038\/s41598-018-28634-0","article-title":"Neuroepithelial control of mucosal inflammation in acute cystitis","volume":"8","author":"Butler","year":"2018","journal-title":"Sci. Rep."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1093\/infdis\/jiv424","article-title":"Uropathogenic Escherichia coli engages Cd14-dependent signaling to enable bladder-macrophage-dependent control of acute urinary tract infection","volume":"213","author":"Carey","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"14572","DOI":"10.1096\/fj.202000760R","article-title":"Restriction of chronic Escherichia coli urinary tract infection depends upon T cell-derived interleukin-17, a deficiency of which predisposes to flagella-driven bacterial persistence","volume":"34","author":"Chamoun","year":"2020","journal-title":"FASEB J."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1016\/j.immuni.2012.10.019","article-title":"Mast cell interleukin-10 drives localized tolerance in chronic bladder infection","volume":"38","author":"Chan","year":"2013","journal-title":"Immunity"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"14012","DOI":"10.1073\/pnas.2436350100","article-title":"Rab27b is associated with fusiform vesicles and may be involved in targeting uroplakins to urothelial apical membranes","volume":"100","author":"Chen","year":"2003","journal-title":"Proc. Natl. Acad. Sci. 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Renal Physiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1016\/j.kint.2017.12.006","article-title":"Interleukin-6\/Stat3 signaling has an essential role in the host antimicrobial response to urinary tract infection","volume":"93","author":"Ching","year":"2018","journal-title":"Kidney Int."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1016\/j.immuni.2016.11.003","article-title":"Loss of bladder epithelium induced by Cytolytic mast cell granules","volume":"45","author":"Choi","year":"2016","journal-title":"Immunity"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e1010950","DOI":"10.1371\/journal.ppat.1010950","article-title":"Bacterial filamentation during urinary tract infections","volume":"18","author":"Coers","year":"2022","journal-title":"PLoS Pathog."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"8308","DOI":"10.1038\/s41467-024-52454-8","article-title":"Nur77 protects the bladder urothelium from intracellular bacterial infection","volume":"15","author":"Collins","year":"2024","journal-title":"Nat. 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Rev."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1186\/s12884-023-06060-z","article-title":"Bacterial profile and prevalence of urinary tract infections in pregnant women in Latin America: a systematic review and meta-analysis","volume":"23","author":"De Souza","year":"2023","journal-title":"BMC Pregnancy Childbirth"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s12979-019-0156-9","article-title":"Elevated urine Il-10 concentrations associate with Escherichia coli persistence in older patients susceptible to recurrent urinary tract infections","volume":"16","author":"Drage","year":"2019","journal-title":"Immun. Ageing"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"781","DOI":"10.4049\/jimmunol.1101231","article-title":"Innate transcriptional networks activated in bladder in response to uropathogenic Escherichia coli drive diverse biological pathways and rapid synthesis of Il-10 for defense against bacterial urinary tract infection","volume":"188","author":"Duell","year":"2012","journal-title":"J. Immunol."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"e1008247","DOI":"10.1371\/journal.ppat.1008247","article-title":"A shear stress micromodel of urinary tract infection by the Escherichia coli producing Dr adhesin","volume":"16","author":"Dumenil","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"3180","DOI":"10.4049\/jimmunol.140.9.3180","article-title":"Host resistance to mucosal gram-negative infection. Susceptibility of lipopolysaccharide nonresponder mice","volume":"140","author":"Ed\u00e9n","year":"1988","journal-title":"J. Immunol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"19651","DOI":"10.1038\/s41598-025-03646-9","article-title":"Serum neutrophil gelatinase associated Lipocalin as a novel biomarker for diagnosing acute pyelonephritis in adults","volume":"15","author":"Elnahal","year":"2025","journal-title":"Sci. Rep."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"6100","DOI":"10.1128\/IAI.00881-06","article-title":"Tumor necrosis factor alpha- and inducible nitric oxide synthase-producing dendritic cells are rapidly recruited to the bladder in urinary tract infection but are dispensable for bacterial clearance","volume":"74","author":"Engel","year":"2006","journal-title":"Infect. 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Infect."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"302","DOI":"10.3389\/fimmu.2015.00302","article-title":"Role of innate T cells in anti-bacterial immunity","volume":"6","author":"Gao","year":"2015","journal-title":"Front. Immunol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"5287","DOI":"10.4049\/jimmunol.165.9.5287","article-title":"Transepithelial neutrophil migration is Cxcr1 dependent in vitro and is defective in Il-8 receptor knockout mice","volume":"165","author":"Godaly","year":"2000","journal-title":"J. Immunol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.ajem.2025.03.038","article-title":"Epidemiology of urinary tract infections in adults among United States emergency departments from 2016 to 2023","volume":"93","author":"Gottlieb","year":"2025","journal-title":"Am. J. Emerg. Med."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"106925","DOI":"10.1016\/j.isci.2023.106925","article-title":"Targeting the Prc2-dependent epigenetic program alleviates urinary tract infections","volume":"26","author":"Guo","year":"2023","journal-title":"iScience"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.chom.2013.11.004","article-title":"Natural killer cell-mediated host defense against uropathogenic E. coli is counteracted by bacterial hemolysinA-dependent killing of Nk cells","volume":"14","author":"Gur","year":"2013","journal-title":"Cell Host Microbe"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1128\/iai.46.3.839-844.1984","article-title":"Difference in susceptibility to gram-negative urinary tract infection between C3H\/HeJ and C3H\/HeN mice","volume":"46","author":"Hagberg","year":"1984","journal-title":"Infect. Immun."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ebiom.2014.10.011","article-title":"Inhibition of Cyclooxygenase-2 prevents chronic and recurrent cystitis","volume":"1","author":"Hannan","year":"2014","journal-title":"EBioMedicine"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1086\/315006","article-title":"Neutrophil recruitment and resistance to urinary tract infection","volume":"180","author":"Haraoka","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"e0031723","DOI":"10.1128\/iai.00317-23","article-title":"Bladder-draining lymph nodes support germinal center B cell responses during urinary tract infection in mice","volume":"91","author":"Hawas","year":"2023","journal-title":"Infect. Immun."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"4702","DOI":"10.1038\/s41598-025-89240-5","article-title":"Epidemiological trends and predictions of urinary tract infections in the global burden of disease study 2021","volume":"15","author":"He","year":"2025","journal-title":"Sci. Rep."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"5156","DOI":"10.3390\/ijms23095156","article-title":"Rnase 7 inhibits Uropathogenic Escherichia coli-induced inflammation in bladder cells under a high-glucose environment by regulating the Jak\/Stat signaling pathway","volume":"23","author":"Ho","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/BF00182044","article-title":"Structure, function, and pathology of proteoglycans and glycosaminoglycans in the urinary-tract","volume":"12","author":"Hurst","year":"1994","journal-title":"World. J. Urol."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2568","DOI":"10.1111\/j.1462-5822.2008.01230.x","article-title":"G-Csf induction early in uropathogenic Escherichia coli infection of the urinary tract modulates host immunity","volume":"10","author":"Ingersoll","year":"2008","journal-title":"Cell. Microbiol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.celrep.2017.06.034","article-title":"Stromal cell-derived factor 1 mediates immune cell attraction upon urinary tract infection","volume":"20","author":"Isaacson","year":"2017","journal-title":"Cell Rep."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"1127","DOI":"10.1038\/s41385-022-00565-0","article-title":"The urothelium: a multi-faceted barrier against a harsh environment","volume":"15","author":"Jafari","year":"2022","journal-title":"Mucosal Immunol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1016\/j.immuni.2014.02.015","article-title":"The humoral pattern recognition molecule Ptx3 is a key component of innate immunity against urinary tract infection","volume":"40","author":"Jaillon","year":"2014","journal-title":"Immunity"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1325","DOI":"10.1016\/j.mucimm.2025.09.001","article-title":"Single cell map of the adult female mouse urethra reveals epithelial and stromal macrophages with distinct functional identities","volume":"18","author":"Jasmine","year":"2025","journal-title":"Mucosal Immunol."},{"key":"ref52","doi-asserted-by":"publisher","first-page":"767175","DOI":"10.3389\/fimmu.2021.767175","article-title":"Neutrophils-from bone marrow to first-line defense of the innate immune system","volume":"12","author":"Kraus","year":"2021","journal-title":"Front. Immunol."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"1154139","DOI":"10.3389\/fped.2023.1154139","article-title":"Neutrophil extracellular traps in urinary tract infection","volume":"11","author":"Krivosikova","year":"2023","journal-title":"Front. Pediatr."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.cellimm.2018.01.018","article-title":"Bladder resident macrophages: Mucosal sentinels","volume":"330","author":"Lacerda Mariano","year":"2018","journal-title":"Cell. Immunol."},{"key":"ref55","doi-asserted-by":"publisher","first-page":"e548","DOI":"10.1093\/infdis\/jiae063","article-title":"Uropathogenic Escherichia coli subverts host Autophagic defenses by stalling Preautophagosomal structures to escape lysosome exocytosis","volume":"230","author":"Li","year":"","journal-title":"J. Infect. Dis."},{"key":"ref56","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.immuni.2025.02.002","article-title":"A bladder-blood immune barrier constituted by suburothelial perivascular macrophages restrains uropathogen dissemination","volume":"58","author":"Li","year":"2025","journal-title":"Immunity"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"925440","DOI":"10.3389\/fcimb.2022.925440","article-title":"Molecular and clinical characterization of hypervirulent Klebsiella pneumoniae isolates from individuals with urinary tract infections","volume":"12","author":"Li","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"114051","DOI":"10.1016\/j.celrep.2024.114051","article-title":"Nucleoside-diphosphate kinase of uropathogenic Escherichia coli inhibits caspase-1-dependent pyroptosis facilitating urinary tract infection","volume":"43","author":"Li","year":"","journal-title":"Cell Rep."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ydbio.2022.11.003","article-title":"Effects of aging on urinary tract epithelial homeostasis and immunity","volume":"493","author":"Ligon","year":"","journal-title":"Dev. Biol."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1097\/JU.0000000000003196","article-title":"Bladder mucosal cystitis Cystica lesions are tertiary lymphoid tissues that correlate with recurrent urinary tract infection frequency in postmenopausal women","volume":"209","author":"Ligon","year":"","journal-title":"J. Urol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1038\/s41385-020-0290-x","article-title":"Single cell and tissue-transcriptomic analysis of murine bladders reveals age- and Tnfalpha-dependent but microbiota-independent tertiary lymphoid tissue formation","volume":"13","author":"Ligon","year":"2020","journal-title":"Mucosal Immunol."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1038\/s41598-022-06052-7","article-title":"The role of caspase-1, caspase-4 and Nlrp3 in regulating the host cell response evoked by uropathogenic Escherichia coli","volume":"12","author":"Lindblad","year":"2022","journal-title":"Sci. Rep."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e1013543","DOI":"10.1371\/journal.ppat.1013543","article-title":"Single-cell analysis reveals an important role of Cd137L+ macrophages in the host response to uropathogenic Escherichia coli infection in the bladder","volume":"21","author":"Liu","year":"2025","journal-title":"PLoS Pathog."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/s41590-020-0689-2","article-title":"Adapt(ed) to repair - T(H)2 immune responses in the bladder promote recurrent infections","volume":"21","author":"Lukens","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref65","doi-asserted-by":"publisher","first-page":"623","DOI":"10.3390\/pathogens12040623","article-title":"Urinary tract infections: the current scenario and future prospects","volume":"12","author":"Mancuso","year":"2023","journal-title":"Pathogens"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"eabc5739","DOI":"10.1126\/sciadv.abc5739","article-title":"Functionally distinct resident macrophage subsets differentially shape responses to infection in the bladder","volume":"6","author":"Mariano","year":"2020","journal-title":"Sci. Adv."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1046\/j.1462-5822.2002.00166.x","article-title":"Requirement of rho-family Gtpases in the invasion of type 1-piliated uropathogenic Escherichia coli","volume":"4","author":"Martinez","year":"2002","journal-title":"Cell. Microbiol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"e180024","DOI":"10.1172\/jci.insight.180024","article-title":"Tamm-Horsfall protein augments neutrophil Netosis during urinary tract infection","volume":"10","author":"Mercado-Evans","year":"2025","journal-title":"JCI Insight"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"1379","DOI":"10.1038\/mt.2010.75","article-title":"FimH can directly activate human and murine natural killer cells via Tlr4","volume":"18","author":"Mian","year":"2010","journal-title":"Mol. Ther."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1016\/j.cell.2015.05.009","article-title":"A Trp Channel senses lysosome neutralization by pathogens to trigger their expulsion","volume":"161","author":"Miao","year":"2015","journal-title":"Cell"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"e1004599","DOI":"10.3390\/pathogens12040623","article-title":"Uropathogenic Escherichia coli superinfection enhances the severity of mouse bladder infection","volume":"11","author":"Monack","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"e1005044","DOI":"10.1371\/journal.ppat.1005044","article-title":"Macrophages subvert adaptive immunity to urinary tract infection","volume":"11","author":"Mora-Bau","year":"2015","journal-title":"PLoS Pathog."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1126\/science.282.5393.1494","article-title":"Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli","volume":"282","author":"Mulvey","year":"1998","journal-title":"Science"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"14170","DOI":"10.1073\/pnas.0602136103","article-title":"Mechanisms of uropathogenic Escherichia coli persistence and eradication from the urinary tract","volume":"103","author":"Mysorekar","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref75","doi-asserted-by":"publisher","first-page":"E871","DOI":"10.1073\/pnas.1500374112","article-title":"Dysregulation Ofescherichia coli\u03b1-hemolysin expression alters the course of acute and persistent urinary tract infection","volume":"112","author":"Nagamatsu","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref76","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1161\/CIRCRESAHA.116.309194","article-title":"Abandoning M1\/M2 for a network model of macrophage function","volume":"119","author":"Nahrendorf","year":"2016","journal-title":"Circ. Res."},{"key":"ref77","doi-asserted-by":"publisher","first-page":"e1011388","DOI":"10.1371\/journal.ppat.1011388","article-title":"\u03b1-Hemolysin promotes uropathogenic E. coli persistence in bladder epithelial cells via abrogating bacteria-harboring lysosome acidification","volume":"19","author":"Naskar","year":"2023","journal-title":"PLoS Pathog."},{"key":"ref78","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/s41577-020-0285-6","article-title":"Defining trained immunity and its role in health and disease","volume":"20","author":"Netea","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"16196","DOI":"10.1038\/nmicrobiol.2016.196","article-title":"A mucosal imprint left by prior Escherichia coli bladder infection sensitizes to recurrent disease","volume":"2","author":"O\u2019Brien","year":"2016","journal-title":"Nat. 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Chem."},{"key":"ref83","doi-asserted-by":"publisher","first-page":"e0326251","DOI":"10.1371\/journal.pone.0326251","article-title":"Iron uptake by Escherichia coli in urinary tract infections and urosepsis","volume":"20","author":"Pakbin","year":"2025","journal-title":"PLoS One"},{"key":"ref84","doi-asserted-by":"publisher","first-page":"110698","DOI":"10.1016\/j.celrep.2022.110698","article-title":"Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection","volume":"39","author":"Pang","year":"2022","journal-title":"Cell Rep."},{"key":"ref85","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1038\/icb.2017.63","article-title":"Tamm-Horsfall glycoprotein engages human Siglec-9 to modulate neutrophil activation in the urinary tract","volume":"95","author":"Patras","year":"2017","journal-title":"Immunol. 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Med."},{"key":"ref90","doi-asserted-by":"publisher","first-page":"e0255423","DOI":"10.1128\/mbio.02554-23","article-title":"Secretory leukocyte protease inhibitor protects against severe urinary tract infection in mice","volume":"15","author":"Rosen","year":"2024","journal-title":"MBio"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"875","DOI":"10.1038\/s41564-023-01346-6","article-title":"Uropathogenic Escherichia coli infection-induced epithelial trained immunity impacts urinary tract disease outcome","volume":"8","author":"Russell","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref92","doi-asserted-by":"publisher","first-page":"10738","DOI":"10.1038\/ncomms10738","article-title":"Catch-bond mechanism of the bacterial adhesin FimH","volume":"7","author":"Sauer","year":"2016","journal-title":"Nat. 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Urol."},{"key":"ref95","doi-asserted-by":"publisher","first-page":"109351","DOI":"10.1016\/j.celrep.2021.109351","article-title":"Early invasion of the bladder wall by solitary bacteria protects Upec from antibiotics and neutrophil swarms in an organoid model","volume":"36","author":"Sharma","year":"2021","journal-title":"Cell Rep."},{"key":"ref96","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.chom.2009.09.004","article-title":"Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues","volume":"6","author":"Shelburne","year":"2009","journal-title":"Cell Host Microbe"},{"key":"ref97","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/nature09851","article-title":"Hedgehog\/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder","volume":"472","author":"Shin","year":"2011","journal-title":"Nature"},{"key":"ref98","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.4049\/jimmunol.0902386","article-title":"The innate immune response to uropathogenic Escherichia coli involves Il-17A in a murine model of urinary tract infection","volume":"184","author":"Sivick","year":"2010","journal-title":"J. Immunol."},{"key":"ref99","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s12894-024-01435-6","article-title":"Mast cell distribution and prevalence in the murine urinary bladder","volume":"24","author":"Smith","year":"2024","journal-title":"BMC Urol."},{"key":"ref100","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.mib.2007.12.001","article-title":"Tlr-mediated immune responses in the urinary tract","volume":"11","author":"Song","year":"2008","journal-title":"Curr. Opin. Microbiol."},{"key":"ref101","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.chom.2007.05.007","article-title":"Tlr4-initiated and camp-mediated abrogation of bacterial invasion of the bladder","volume":"1","author":"Song","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref102","doi-asserted-by":"publisher","first-page":"7081","DOI":"10.1038\/s41467-023-42625-4","article-title":"Tissue-resident B cells orchestrate macrophage polarisation and function","volume":"14","author":"Suchanek","year":"2023","journal-title":"Nat. Commun."},{"key":"ref103","doi-asserted-by":"publisher","first-page":"1093922","DOI":"10.3389\/fmicb.2023.1093922","article-title":"Evasion of toll-like receptor recognition by Escherichia coli is mediated via population level regulation of flagellin production","volume":"14","author":"Tan","year":"2023","journal-title":"Front. Microbiol."},{"key":"ref104","doi-asserted-by":"publisher","first-page":"e20230570","DOI":"10.1084\/jem.20230570","article-title":"Landscape of mast cell populations across organs in mice and humans","volume":"220","author":"Tauber","year":"2023","journal-title":"J. Exp. Med."},{"key":"ref105","doi-asserted-by":"publisher","first-page":"e193793","DOI":"10.1172\/JCI193793","article-title":"Macrophage transition to a myofibroblast state drives fibrotic disease in uropathogenic E. coli-induced epididymo-orchitis","volume":"135","author":"Wang","year":"2025","journal-title":"J. Clin. 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