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dc.contributor.author
Hoffmann, Claudia
dc.contributor.author
Galle, Marlies
dc.contributor.author
Dilling, Sabrina
dc.contributor.author
Käppeli, Rina
dc.contributor.author
Müller, Andreas J.
dc.contributor.author
Songhet, Pascal
dc.contributor.author
Beyaert, Rudi
dc.contributor.author
Hardt, Wolf-Dietrich
dc.date.accessioned
2018-09-20T12:36:31Z
dc.date.available
2017-06-09T05:22:41Z
dc.date.available
2018-09-20T12:36:31Z
dc.date.issued
2010-08-30
dc.identifier.issn
1932-6203
dc.identifier.other
10.1371/journal.pone.0012477
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/22234
dc.identifier.doi
10.3929/ethz-b-000022234
dc.description.abstract
The innate immune system is of vital importance for protection against infectious pathogens. Inflammasome mediated caspase-1 activation and subsequent release of pro-inflammatory cytokines like IL-1β and IL-18 is an important arm of the innate immune system. Salmonella enterica subspecies 1 serovar Typhimurium (S. Typhimurium, SL1344) is an enteropathogenic bacterium causing diarrheal diseases. Different reports have shown that in macrophages, S. Typhimurium may activate caspase-1 by at least three different types of stimuli: flagellin, the type III secretion system 1 (T1) and the T1 effector protein SopE. However, the relative importance and interdependence of the different factors in caspase-1 activation is still a matter of debate. Here, we have analyzed their relative contributions to caspase-1 activation in LPS-pretreated RAW264.7 macrophages. Using flagellar mutants (fliGHI, flgK) and centrifugation to mediate pathogen-host cell contact, we show that flagellins account for a small part of the caspase-1 activation in RAW264.7 cells. In addition, functional flagella are of key importance for motility and host cell attachment which is a prerequisite for mediating caspase-1 activation via these three stimuli. Using site directed mutants lacking several T1 effector proteins and flagellin expression, we found that SopE elicits caspase-1 activation even when flagellins are absent. In contrast, disruption of essential genes of the T1 protein injection system (invG, sipB) completely abolished caspase-1 activation. However, a robust level of caspase-1 activation is retained by the T1 system (or unidentified T1 effectors) in the absence of flagellin and SopE. T1-mediated inflammasome activation is in line with recent work by others and suggests that the T1 system itself may represent the basic caspase-1 activating stimulus in RAW264.7 macrophages which is further enhanced independently by SopE and/or flagellin.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
PLoS
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/3.0/
dc.title
In Macrophages, Caspase-1 Activation by SopE and the Type III Secretion System-1 of S. Typhimurium Can Proceed in the Absence of Flagellin
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 3.0 Unported
ethz.journal.title
PLoS ONE
ethz.journal.volume
5
en_US
ethz.journal.issue
8
en_US
ethz.journal.abbreviated
PLoS ONE
ethz.pages.start
e12477
en_US
ethz.size
11 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.publication.place
Lawrence, KS, USA
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::02520 - Institut für Mikrobiologie / Institute of Microbiology::03589 - Hardt, Wolf-Dietrich / Hardt, Wolf-Dietrich
ethz.date.deposited
2017-06-09T05:22:47Z
ethz.source
ECIT
ethz.identifier.importid
imp59364cfb9ab4455505
ethz.ecitpid
pub:37051
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T21:06:02Z
ethz.rosetta.lastUpdated
2018-11-08T02:39:52Z
ethz.rosetta.versionExported
true
ethz.COinS
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