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2022 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 40, no 6, article id 111173Article in journal (Refereed) Published
Abstract [en]
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 Ca2+ 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.
Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
mechanosensing, immune detection, danger signals, invasive pathogens, Shigella, Listeria, plasma membrane ruffles, PIEZO1, extracellular ATP, intestinal epithelial cells
National Category
Cell and Molecular Biology Immunology in the medical area Microbiology in the medical area
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-198648 (URN)10.1016/j.celrep.2022.111173 (DOI)000881382400003 ()2-s2.0-85135700972 (Scopus ID)
Funder
Knut and Alice Wallenberg Foundation, KAW 2015.0225The Kempe Foundations, JCK-1528The Kempe Foundations, SMK-1859The Kempe Foundations, JCK-2031.3Swedish Research Council, 2016-06598Carl Tryggers foundation , CTS 18-65The Kempe Foundations, SMK-1860The Kempe Foundations, SMK-1532.2Swedish Society for Medical Research (SSMF), PD20-0022
2022-08-152022-08-152024-01-17Bibliographically approved