%0 Journal Article %T Macrophages Subvert Adaptive Immunity to Urinary Tract Infection %+ Immunobiologie des Cellules Dendritiques %+ Department of Gene and Cell Medicine and the Immunology Institute %+ Department of Molecular Cell Biology [Amsterdam UMC] %A Mora Bau, Gabriela %A Platt, Am %A van Rooijen, N. %A Randolph, Gwendalyn J %A Albert, Matthew L %A Ingersoll, Molly A %Z This project was supported in part by funding from a Ruth Chemers Neustein Postdoctoral Fellowship award, European Union Seventh Framework Programme Marie Curie Action (PCIG11-GA- 2012-3221170, and the Immuno-Oncology LabEx (MAI). GMB is a scholar from the Pasteur-Paris University (PPU) International PhD program. GJR was supported by National Institutes of Health AI049653. %< avec comité de lecture %@ 1553-7366 %J PLoS Pathogens %I Public Library of Science %V 11 %N 7 %P e1005044 %8 2015-07-16 %D 2015 %R 10.1371/journal.ppat.1005044 %M 26182347 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X Urinary tract infection (UTI) is one of the most common bacterial infections with frequent recurrence being a major medical challenge. Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity. Here, we establish conclusive evidence that an adaptive immune response is generated during UTI, yet this response does not establish sterilizing immunity. To investigate the underlying deficiency, we delineated the naïve bladder immune cell compartment, identifying resident macrophages as the most populous immune cell. To evaluate their impact on the establishment of adaptive immune responses following infection, we measured bacterial clearance in mice depleted of either circulating monocytes, which give rise to macrophages, or bladder resident macrophages. Surprisingly, mice depleted of resident macrophages, prior to primary infection, exhibited a nearly 2-log reduction in bacterial burden following secondary challenge compared to untreated animals. This increased bacterial clearance, in the context of a challenge infection, was dependent on lymphocytes. Macrophages were the predominant antigen presenting cell to acquire bacteria post-infection and in their absence, bacterial uptake by dendritic cells was increased almost 2-fold. These data suggest that bacterial uptake by tissue macrophages impedes development of adaptive immune responses during UTI, revealing a novel target for enhancing host responses to bacterial infection of the bladder. %G English %2 https://pasteur.hal.science/pasteur-01380952/document %2 https://pasteur.hal.science/pasteur-01380952/file/journal.ppat.1005044.pdf %L pasteur-01380952 %U https://pasteur.hal.science/pasteur-01380952 %~ INSERM %~ PASTEUR %~ ATP-IMMUN %~ ANR