Type IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila

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dc.contributor.authorShin, Sunny
dc.contributor.authorCase, Christopher L
dc.contributor.authorArcher, Kristina A
dc.contributor.authorNogueira, Catarina V
dc.contributor.authorKobayashi, Koichi S
dc.contributor.authorFlavell, Richard A
dc.contributor.authorRoy, Craig R
dc.contributor.authorZamboni, Dario S
dc.date2023-05-17T11:47:36.000
dc.date.accessioned2023-05-22T23:55:51Z
dc.date.available2023-05-22T23:55:51Z
dc.date.issued2008-11-28
dc.date.submitted2015-06-16T11:26:33-07:00
dc.description.abstractThe immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs) detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs) sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS), induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-κB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.
dc.description.commentsAt the time of publication, author Sunny Shin was affiliated with Yale University School of Medicine. Currently, she is a faculty member at the Perelman School of Medicine at the University of Pennsylvania.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/40575
dc.legacy.articleid1001
dc.legacy.fields10.1371/journal.ppat.1000220
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1001&context=microbiology&unstamped=1
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (https://creativecommons.org/licenses/by/3.0/us/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.beginpagee1000220
dc.source.issue4
dc.source.issue11
dc.source.journalDepartment of Microbiology Papers
dc.source.journaltitlePLoS Pathogens
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume4
dc.subject.otherlegionella pneumophila
dc.subject.othermacrophages
dc.subject.otherMAPK signaling cascades
dc.subject.othercytokines
dc.subject.otherbacterial pathogens
dc.subject.otherDNA transcription
dc.subject.otherimmune receptor signaling
dc.subject.otherimmune response
dc.subject.otherImmunology and Infectious Disease
dc.subject.otherMicrobiology
dc.subject.otherPathogenic Microbiology
dc.titleType IV Secretion-Dependent Activation of Host MAP Kinases Induces an Increased Proinflammatory Cytokine Response to Legionella pneumophila
dc.typeArticle
digcom.identifiermicrobiology/4
digcom.identifier.contextkey7223597
digcom.identifier.submissionpathmicrobiology/4
digcom.typearticle
dspace.entity.typePublication
relation.isAuthorOfPublication28557f46-a32a-44f5-a314-3c477772e375
relation.isAuthorOfPublication.latestForDiscovery28557f46-a32a-44f5-a314-3c477772e375
upenn.schoolDepartmentCenterDepartment of Microbiology Papers
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