title: Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules.
abstract: Programmed death and shedding of epithelial cells is a powerful defense mechanism to reduce bacterial burden during infection but this activity cannot be indiscriminate because of the critical barrier function of the epithelium. We report that during cystitis, shedding of infected bladder epithelial cells (BECs) was preceded by the recruitment of mast cells (MCs) directly underneath the superficial epithelium where they docked and extruded their granules. MCs were responding to interleukin-1β (IL-1β) secreted by BECs after inflammasome and caspase-1 signaling. Upon uptake of granule-associated chymase (mouse MC protease 4 [mMCPT4]), BECs underwent caspase-1-associated cytolysis and exfoliation. Thus, infected epithelial cells require a specific cue for cytolysis from recruited sentinel inflammatory cells before shedding.
authors.affiliation: Department of Pathology, Duke University, Durham, NC 27710, USA. Electronic address: haewoong.choi@duke.edu.
authors.forename: Hae Woong
authors.initials: HW
authors.lastname: Choi
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Samantha E
authors.initials: SE
authors.lastname: Bowen
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Miao
authors.affiliation: Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore.
authors.forename: Cheryl Y
authors.initials: CY
authors.lastname: Chan
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Miao
authors.affiliation: Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 75007 Uppsala, Sweden.
authors.forename: Magnus
authors.initials: M
authors.lastname: Abrink
authors.affiliation: Departments of Large Animal Clinical Sciences and Physiology, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Moeser
authors.affiliation: Department of Pathology, Duke University, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA; Department of Immunology, Duke University, Durham, NC 27710, USA; Program in Emerging Infectious Diseases, Duke-National University of Singapore, Singapore 169857, Singapore.
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
mesh_terms: D000818:Animals; D015550:Cell Degranulation / Q000276:immunology; D002460:Cell Line; D053818:Chymases / Q000276:immunology*; D003594:Cytoplasmic Granules / Q000737:chemistry; D003603:Cytotoxins / Q000276:immunology*; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014552:Urinary Tract Infections / Q000276:immunology*
chemical_list: D003603:Cytotoxins; D053818:Chymases
keywords: IL-1β; bladder epithelial cells; caspase 1; chymase; cytolysis; cytolytic granules; exfoliation; inflammasome; mast cells; uropathogenic E. coli