title: Macrophages Subvert Adaptive Immunity to Urinary Tract Infection.
abstract: 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.
authors.affiliation: Unité d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur and INSERM U818, Paris, France.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Mora-Bau
authors.affiliation: Department of Gene and Cell Medicine and the Immunology Institute, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Platt
authors.affiliation: Department of Molecular Cell Biology, Free University Medical Center, Amsterdam, The Netherlands.
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.affiliation: Department of Gene and Cell Medicine and the Immunology Institute, Mount Sinai School of Medicine, New York, New York, United States of America.
authors.forename: Gwendalyn J
authors.initials: GJ
authors.lastname: Randolph
authors.affiliation: Unité d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur and INSERM U818, Paris, France.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert
authors.affiliation: Unité d'Immunobiologie des Cellules Dendritiques, Department of Immunology, Institut Pasteur and INSERM U818, Paris, France.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Ingersoll
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D004927:Escherichia coli Infections / Q000276:immunology; D005260:Female; D007113:Immunity, Innate / Q000276:immunology; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D008810:Mice, Inbred C57BL; D014552:Urinary Tract Infections / Q000276:immunology* / Q000382:microbiology