Infection-induced membrane ruffling initiates danger and immune signaling via the mechanosensor PIEZO1

Lalitha Tadala, Dorothee Langenbach, Mirjam Dannborg, Ramón Cervantes-Rivera, Atin Sharma, Kevin Vieth, Lisa M. Rieckmann, Alkwin Wanders, David A. Cisneros, Andrea Puhar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)
33 Downloads (Pure)

Abstract

Microorganisms are generally sensed by receptors recognizing microbial molecules, which evoke changes in cellular activities and gene expression. Bacterial pathogens induce secretion of the danger signal ATP as an early alert response of intestinal epithelial cells, initiating overt inflammation. However, what triggers ATP secretion during infection is unclear. Here we show that the inherently mechanosensitive plasma membrane channel PIEZO1 acts as a sensor for bacterial entry. PIEZO1 is mechanically activated by invasion-induced membrane ruffles upstream of Ca(2+) influx and ATP secretion. Mimicking mechanical stimuli of pathogen uptake with sterile beads equally elicits ATP secretion. Chemical or genetic PIEZO1 inactivation inhibits mechanically induced ATP secretion. Moreover, chemical or mechanical PIEZO1 activation evokes gene expression in immune and barrier pathways. Thus, mechanosensation of invasion-induced plasma membrane distortion initiates immune signaling upon infection, independently of detection of microbial molecules. Hence, PIEZO1-dependent detection of infection is driven by physical signals instead of chemical ligands.

Original languageEnglish
Article number111173
Number of pages28
JournalCell Reports
Volume40
Issue number6
DOIs
Publication statusPublished - 09 Aug 2022
Externally publishedYes

Keywords

  • Shigella
  • *Ion Channels/metabolism
  • *Signal Transduction
  • Adenosine Triphosphate/metabolism
  • Biological Transport
  • Cell Membrane/metabolism
  • CP: Cell biology
  • CP: Immunology
  • danger signals
  • extracellular ATP
  • immune detection
  • intestinal epithelial cells
  • invasive pathogens
  • Listeria
  • mechanosensing
  • Mechanotransduction, Cellular/physiology
  • Piezo1
  • plasma membrane ruffles

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