Listeria monocytogenes desensitizes immune cells to subsequent Ca2+ signaling via listeriolysin O-induced depletion of intracellular Ca2+ stores.

2.50
Hdl Handle:
http://hdl.handle.net/10033/28252
Title:
Listeria monocytogenes desensitizes immune cells to subsequent Ca2+ signaling via listeriolysin O-induced depletion of intracellular Ca2+ stores.
Authors:
Gekara, Nelson O; Groebe, Lothar; Viegas, Nuno; Weiss, Siegfried
Abstract:
Listeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, is a prototype of the cholesterol-dependent cytolysins (CDCs) secreted by several pathogenic and nonpathogenic gram-positive bacteria. In addition to mediating the escape of the bacterium into the cytosol, this toxin is generally believed to be a central player in host-pathogen interactions during L. monocytogenes infection. LLO triggers the influx of Ca(2+) into host cells as well as the release of Ca(2+) from intracellular stores. Thus, many of the cellular responses induced by LLO are related to calcium signaling. Interestingly, in this study, we report that prolonged exposure to LLO desensitizes cells to Ca(2+) mobilization upon subsequent stimulations with LLO. Cells preexposed to LLO-positive L. monocytogenes but not to the LLO-deficient Deltahly mutant were found to be highly refractory to Ca(2+) induction in response to receptor-mediated stimulation. Such cells also exhibited diminished Ca(2+) signals in response to stimulation with LLO and thapsigargin. The presented results suggest that this phenomenon is due to the depletion of intracellular Ca(2+) stores. The ability of LLO to desensitize immune cells provides a significant hint about the possible role played by CDCs in the evasion of the immune system by bacterial pathogens.
Affiliation:
Department of Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. nelson.gekara@helmholtz-hzi.de
Citation:
Listeria monocytogenes desensitizes immune cells to subsequent Ca2+ signaling via listeriolysin O-induced depletion of intracellular Ca2+ stores. 2008, 76 (2):857-62 Infect. Immun.
Journal:
Infection and immunity
Issue Date:
Feb-2008
URI:
http://hdl.handle.net/10033/28252
DOI:
10.1128/IAI.00622-07
PubMed ID:
18056478
Type:
Article
Language:
en
ISSN:
1098-5522
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorGekara, Nelson O-
dc.contributor.authorGroebe, Lothar-
dc.contributor.authorViegas, Nuno-
dc.contributor.authorWeiss, Siegfried-
dc.date.accessioned2008-05-27T09:47:50Z-
dc.date.available2008-05-27T09:47:50Z-
dc.date.issued2008-02-
dc.identifier.citationListeria monocytogenes desensitizes immune cells to subsequent Ca2+ signaling via listeriolysin O-induced depletion of intracellular Ca2+ stores. 2008, 76 (2):857-62 Infect. Immun.en
dc.identifier.issn1098-5522-
dc.identifier.pmid18056478-
dc.identifier.doi10.1128/IAI.00622-07-
dc.identifier.urihttp://hdl.handle.net/10033/28252-
dc.description.abstractListeriolysin O (LLO), the pore-forming toxin of Listeria monocytogenes, is a prototype of the cholesterol-dependent cytolysins (CDCs) secreted by several pathogenic and nonpathogenic gram-positive bacteria. In addition to mediating the escape of the bacterium into the cytosol, this toxin is generally believed to be a central player in host-pathogen interactions during L. monocytogenes infection. LLO triggers the influx of Ca(2+) into host cells as well as the release of Ca(2+) from intracellular stores. Thus, many of the cellular responses induced by LLO are related to calcium signaling. Interestingly, in this study, we report that prolonged exposure to LLO desensitizes cells to Ca(2+) mobilization upon subsequent stimulations with LLO. Cells preexposed to LLO-positive L. monocytogenes but not to the LLO-deficient Deltahly mutant were found to be highly refractory to Ca(2+) induction in response to receptor-mediated stimulation. Such cells also exhibited diminished Ca(2+) signals in response to stimulation with LLO and thapsigargin. The presented results suggest that this phenomenon is due to the depletion of intracellular Ca(2+) stores. The ability of LLO to desensitize immune cells provides a significant hint about the possible role played by CDCs in the evasion of the immune system by bacterial pathogens.en
dc.language.isoenen
dc.subject.meshAnimalsen
dc.subject.meshBacterial Toxinsen
dc.subject.meshCalciumen
dc.subject.meshCalcium Signalingen
dc.subject.meshCells, Cultureden
dc.subject.meshHeat-Shock Proteinsen
dc.subject.meshHemolysin Proteinsen
dc.subject.meshListeria monocytogenesen
dc.subject.meshMast Cellsen
dc.subject.meshMiceen
dc.titleListeria monocytogenes desensitizes immune cells to subsequent Ca2+ signaling via listeriolysin O-induced depletion of intracellular Ca2+ stores.en
dc.typeArticleen
dc.contributor.departmentDepartment of Molecular Immunology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany. nelson.gekara@helmholtz-hzi.deen
dc.identifier.journalInfection and immunityen
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