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

Autor:	Tadala L; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Langenbach D; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Dannborg M; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Cervantes-Rivera R; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Sharma A; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Vieth K; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Rieckmann LM; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Wanders A; Department of Medical Biosciences, Umeå University, 901 87 Umeå, Sweden; Department of Pathology, Aalborg University Hospital, 9100 Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, 9000 Aalborg, Denmark., Cisneros DA; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden., Puhar A; The Laboratory for Molecular Infection Medicine Sweden (MIMS), 901 87, Umeå, Sweden; Umeå Centre for Microbial Research (UCMR), 901 87 Umeå, Sweden; Department of Molecular Biology, Umeå University, 901 87 Umeå, Sweden. Electronic address: andrea.puhar@umu.se.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Aug 09; Vol. 40 (6), pp. 111173.
DOI:	10.1016/j.celrep.2022.111173
Abstrakt:	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. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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