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dc.contributor.author
Kellogg, Ryan A.
dc.contributor.author
Tian, Chengzhe
dc.contributor.author
Etzrodt, Martin
dc.contributor.author
Tay, Savaş
dc.date.accessioned
2018-09-19T09:12:50Z
dc.date.available
2017-06-12T20:46:44Z
dc.date.available
2018-09-19T09:12:50Z
dc.date.issued
2017-04
dc.identifier.other
10.1016/j.celrep.2017.03.027
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/130292
dc.identifier.doi
10.3929/ethz-b-000130292
dc.description.abstract
Cells receive a multitude of signals from the environment, but how they process simultaneous signaling inputs is not well understood. Response to infection, for example, involves parallel activation of multiple Toll-like receptors (TLRs) that converge on the nuclear factor κB (NF-κB) pathway. Although we increasingly understand inflammatory responses for isolated signals, it is not clear how cells process multiple signals that co-occur in physiological settings. We therefore examined a bacterial infection scenario involving co-stimulation of TLR4 and TLR2. Independent stimulation of these receptors induced distinct NF-κB dynamic profiles, although surprisingly, under co-stimulation, single cells continued to show ligand-specific dynamic responses characteristic of TLR2 or TLR4 signaling rather than a mixed response, comprising a cellular decision that we term “non-integrative” processing. Iterating modeling and microfluidic experiments revealed that non-integrative processing occurred through interaction of switch-like NF-κB activation, receptor-specific processing timescales, cell-to-cell variability, and TLR cross-tolerance mediated by multilayer negative feedback.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject
Digital
en_US
dc.subject
Dynamics
en_US
dc.subject
Immunity
en_US
dc.subject
Information processing
en_US
dc.subject
Live-cell imaging
en_US
dc.subject
Microfluidics
en_US
dc.subject
Signaling
en_US
dc.subject
Single cell
en_US
dc.subject
Synergy
en_US
dc.subject
toll-like receptors
en_US
dc.title
Cellular Decision Making by Non-Integrative Processing of TLR Inputs
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2017-04-04
ethz.journal.title
Cell Reports
ethz.journal.volume
19
en_US
ethz.journal.issue
1
en_US
ethz.pages.start
125
en_US
ethz.pages.end
135
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
007612702
ethz.publication.place
Amsterdam
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-12T20:47:14Z
ethz.source
ECIT
ethz.identifier.importid
imp5936556583d2013739
ethz.ecitpid
pub:193298
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-15T17:41:50Z
ethz.rosetta.lastUpdated
2018-09-19T09:12:57Z
ethz.rosetta.versionExported
true
ethz.COinS
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