[PDF][PDF] Loss of bladder epithelium induced by cytolytic mast cell granules

HW Choi, SE Bowen, Y Miao, CY Chan, EA Miao… - Immunity, 2016 - cell.com
Immunity, 2016cell.com
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 …
Summary
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.
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