Loss of Bladder Epithelium Induced by Cytolytic Mast Cell Granules

Immunity. 2016 Dec 20;45(6):1258-1269. doi: 10.1016/j.immuni.2016.11.003. Epub 2016 Dec 6.

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.

Keywords: IL-1β; bladder epithelial cells; caspase 1; chymase; cytolysis; cytolytic granules; exfoliation; inflammasome; mast cells; uropathogenic E. coli.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Degranulation / immunology
  • Cell Line
  • Chymases / immunology*
  • Cytoplasmic Granules / chemistry
  • Cytotoxins / immunology*
  • Epithelial Cells / microbiology*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • Mast Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Urinary Tract Infections / immunology*

Substances

  • Cytotoxins
  • Chymases