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In order to identify the key facets of the host response that influence pathogen clearance and tissue damage, single-cell RNA sequencing was used to investigate the transcriptomic changes of immune cells in mouse bladder after UPEC infection. Single-cell analysis revealed significant elevated CD137L expression in macrophages and dendritic cells in bladder after UPEC infection. CD137L defines a macrophage population in bladder that is important for the host response to UPEC infection. Deletion of CD137L in macrophages resulted in severe bacterial burden and bladder inflammation during the acute stage of UPEC infection. Further study demonstrated that the crucial role of CD137L<jats:sup>+<\/jats:sup> macrophages in protecting against UPEC infection might be mediated by Tregs, which express high levels of CD137 (the receptor for CD137L). Deletion of CD137L<jats:sup>+<\/jats:sup> macrophages decreased Treg cells and led to a reduction in inhibitory factors such as CTLA-4 and PD-1 on Tregs. Deletion of Tregs using Foxp3DTR mice also aggravated inflammatory reactions, bacterial load, and urothelial destruction during the acute phase of UPEC infection. Similarly, the deletion of CD137 in Tregs resulted in a decrease in these inhibitory factors on Tregs, causing more severe bladder inflammation during UPEC infection. These results illuminate the immune landscape of the bladder infected by UPEC and highlight the crucial role of CD137L<jats:sup>+<\/jats:sup> macrophages during UPEC infection in bladder. CD137L<jats:sup>+<\/jats:sup> macrophages might prevent excessive inflammatory response during the host response to UPEC infection by regulating Tregs.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013543","type":"journal-article","created":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T17:21:16Z","timestamp":1759512076000},"page":"e1013543","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Single-cell analysis reveals an important role of CD137L+ macrophages in the host response to uropathogenic Escherichia coli infection in the 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Gao","year":"2022","journal-title":"J Inflamm Res"},{"issue":"1","key":"ppat.1013543.ref020","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1002\/nau.24205","article-title":"Cannabinoid receptor 2 activation decreases severity of cyclophosphamide-induced cystitis via regulating autophagy","volume":"39","author":"Q Liu","year":"2020","journal-title":"Neurourol Urodyn"},{"issue":"10","key":"ppat.1013543.ref021","doi-asserted-by":"crossref","first-page":"114859","DOI":"10.1016\/j.celrep.2024.114859","article-title":"ILC2-derived CGRP triggers acute inflammation and nociceptive responses in bacterial cystitis","volume":"43","author":"Z Yang","year":"2024","journal-title":"Cell Rep"},{"issue":"7","key":"ppat.1013543.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005044","article-title":"Macrophages Subvert Adaptive Immunity to Urinary Tract Infection","volume":"11","author":"G Mora-Bau","year":"2015","journal-title":"PLoS 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novel series of biologically active compounds formed from arachidonic acid in human leukocytes","volume":"81","author":"CN Serhan","year":"1984","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"4","key":"ppat.1013543.ref027","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1084\/jem.20031325","article-title":"Exogenous pathogen and plant 15-lipoxygenase initiate endogenous lipoxin A4 biosynthesis","volume":"199","author":"GL Bannenberg","year":"2004","journal-title":"J Exp Med"},{"issue":"7168","key":"ppat.1013543.ref028","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nature06307","article-title":"Identification of Tim4 as a phosphatidylserine receptor","volume":"450","author":"M Miyanishi","year":"2007","journal-title":"Nature"},{"issue":"26","key":"ppat.1013543.ref029","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2011-04-345330","article-title":"Transcriptomic analyses of murine resolution-phase macrophages","volume":"118","author":"MJ Stables","year":"2011","journal-title":"Blood"},{"issue":"10","key":"ppat.1013543.ref030","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1161\/CIRCULATIONAHA.107.699173","article-title":"CD137 is expressed in human atherosclerosis and promotes development of plaque inflammation in hypercholesterolemic mice","volume":"117","author":"PS Olofsson","year":"2008","journal-title":"Circulation"},{"issue":"1","key":"ppat.1013543.ref031","article-title":"Reverse signaling through the costimulatory ligand CD137L in epithelial cells is essential for natural killer cell-mediated acute tissue inflammation","volume":"109","author":"HJ Kim","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1013543.ref032","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1146\/annurev-immunol-101220-032117","article-title":"Tissue Immunity in the Bladder","volume":"40","author":"GS Bowyer","year":"2022","journal-title":"Annu Rev Immunol"},{"issue":"5","key":"ppat.1013543.ref033","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4110\/in.2012.12.5.176","article-title":"Regulation of Inflammation by Bidirectional Signaling through CD137 and Its Ligand","volume":"12","author":"B Kwon","year":"2012","journal-title":"Immune Netw"},{"key":"ppat.1013543.ref034","doi-asserted-by":"crossref","first-page":"683680","DOI":"10.3389\/fimmu.2021.683680","article-title":"BHLHE40 Regulates IL-10 and IFN-\u03b3 Production in T Cells but Does Not Interfere With Human Type 1 Regulatory T Cell Differentiation","volume":"12","author":"MJ Uyeda","year":"2021","journal-title":"Front Immunol"},{"issue":"4","key":"ppat.1013543.ref035","doi-asserted-by":"crossref","first-page":"690","DOI":"10.3390\/nano12040690","article-title":"Cellular Uptake of Silica and Gold Nanoparticles Induces Early Activation of Nuclear Receptor NR4A1","volume":"12","author":"M Sousa de Almeida","year":"2022","journal-title":"Nanomaterials (Basel)"},{"issue":"5","key":"ppat.1013543.ref036","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1165\/rcmb.2019-0443OC","article-title":"DNGR1-Cre-mediated Deletion of Tnfaip3\/A20 in Conventional Dendritic Cells Induces Pulmonary Hypertension in Mice","volume":"63","author":"T Koudstaal","year":"2020","journal-title":"Am J Respir Cell Mol Biol"},{"key":"ppat.1013543.ref037","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1146\/annurev.immunol.23.021704.115839","article-title":"TNF\/TNFR family members in costimulation of T cell responses","volume":"23","author":"TH Watts","year":"2005","journal-title":"Annu Rev Immunol"},{"issue":"8","key":"ppat.1013543.ref038","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.it.2005.06.003","article-title":"Interfacing T-cell effector and regulatory function through CD137 (4-1BB) co-stimulation","volume":"26","author":"LM Myers","year":"2005","journal-title":"Trends 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Shao","year":"2011","journal-title":"J Leukoc Biol"},{"issue":"3","key":"ppat.1013543.ref046","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/eji.201445174","article-title":"Inhibition of 4-1BBL-regulated TLR response in macrophages ameliorates endotoxin-induced sepsis in mice","volume":"45","author":"BR Bang","year":"2015","journal-title":"Eur J Immunol"},{"issue":"4","key":"ppat.1013543.ref047","doi-asserted-by":"crossref","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":"AJ Carey","year":"2016","journal-title":"J Infect Dis"},{"issue":"3","key":"ppat.1013543.ref048","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2014.01.006","article-title":"Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium","volume":"156","author":"M Schiwon","year":"2014","journal-title":"Cell"},{"issue":"295","key":"ppat.1013543.ref049","article-title":"The TNF family member 4-1BBL sustains inflammation by interacting with TLR signaling components during late-phase activation","volume":"6","author":"J Ma","year":"2013","journal-title":"Sci Signal"},{"issue":"7","key":"ppat.1013543.ref050","doi-asserted-by":"crossref","first-page":"1892","DOI":"10.4049\/jimmunol.1900983","article-title":"4-1BBL Regulates the Polarization of Macrophages, and Inhibition of 4-1BBL Signaling Alleviates Imiquimod-Induced Psoriasis","volume":"204","author":"H Miki","year":"2020","journal-title":"J Immunol"},{"issue":"6","key":"ppat.1013543.ref051","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/ni1471","article-title":"Cell surface 4-1BBL mediates sequential signaling pathways \u201cdownstream\u201d of TLR and is required for sustained TNF production in macrophages","volume":"8","author":"YJ Kang","year":"2007","journal-title":"Nat Immunol"},{"issue":"1","key":"ppat.1013543.ref052","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/imr.12621","article-title":"Overview of the IL-1 family in innate inflammation and acquired immunity","volume":"281","author":"CA Dinarello","year":"2018","journal-title":"Immunol Rev"},{"issue":"6","key":"ppat.1013543.ref053","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.immuni.2011.12.002","article-title":"Innate and adaptive interferons suppress IL-1\u03b1 and IL-1\u03b2 production by distinct pulmonary myeloid subsets during Mycobacterium tuberculosis infection","volume":"35","author":"KD Mayer-Barber","year":"2011","journal-title":"Immunity"},{"key":"ppat.1013543.ref054","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.immunol.021908.132612","article-title":"Immunological and inflammatory functions of the interleukin-1 family","volume":"27","author":"CA Dinarello","year":"2009","journal-title":"Annu Rev Immunol"},{"issue":"83","key":"ppat.1013543.ref055","doi-asserted-by":"crossref","DOI":"10.1126\/sciimmunol.abn4332","article-title":"Tissue-resident memory T cells mediate mucosal immunity to recurrent urinary tract infection","volume":"8","author":"M Rousseau","year":"2023","journal-title":"Sci Immunol"},{"issue":"18","key":"ppat.1013543.ref056","article-title":"Multimodal Single-Cell Analyses Outline the Immune Microenvironment and Therapeutic Effectors of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"9","author":"F Su","year":"2022","journal-title":"Adv Sci (Weinh)"},{"issue":"8","key":"ppat.1013543.ref057","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S1047-2797(00)00072-7","article-title":"Urinary tract infection: self-reported incidence and associated costs","volume":"10","author":"B Foxman","year":"2000","journal-title":"Ann 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