Aggregatibacter Actinomycetemcomitans Cytolethal Distending Toxin Activates the NLRP3 Inflammasome in Human Macrophages, Leading to the Release of Proinflammatory Cytokines

Simple item page
dc.contributor.authorShenker, Bruce J.
dc.contributor.authorOjcius, David M.
dc.contributor.authorWalker, Lisa P.
dc.contributor.authorZekavat, Ali
dc.contributor.authorScuron, Monika Damek
dc.contributor.authorBoesze-Battaglia, Kathleen
dc.date2023-05-18T03:53:47.000
dc.date.accessioned2023-05-22T13:15:16Z
dc.date.available2023-05-22T13:15:16Z
dc.date.issued2015-01-01
dc.date.submitted2022-10-18T08:28:11-07:00
dc.description.abstractThe cytolethal distending toxin (Cdt) is produced from a number of bacteria capable of causing infection and inflammatory disease. Our previous studies with Actinobacillus actinomycetemcomitans Cdt demonstrate not only that the active toxin subunit functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase but also that macrophages exposed to the toxin were stimulated to produce proinflammatory cytokines. We now demonstrate that the Cdt-induced proinflammatory response involves the activation of the NLRP3 inflammasome. Specific inhibitors and short hairpin RNA (shRNA) were employed to demonstrate requirements for NLRP3 and ASC as well as caspase-1. Furthermore, Cdt-mediated inflammasome activation is dependent upon upstream signals, including reactive oxygen species (ROS) generation and Cdt-induced increases in extracellular ATP levels. Increases in extracellular ATP levels contribute to the activation of the P2X7 purinergic receptor, leading to K+ efflux. The relationship between the abilities of the active toxin subunit CdtB to function as a lipid phosphatase, activate the NLRP3 inflammasome, and induce a proinflammatory cytokine response is discussed. These studies provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms such as Aggregatibacter actinomycetemcomitans. © 2015, American Society for Microbiology.
dc.identifier.urihttps://repository.upenn.edu/handle/20.500.14332/9119
dc.legacy.articleid1623
dc.legacy.fields10.1128/IAI.03132-14
dc.legacy.fulltexturlhttps://repository.upenn.edu/cgi/viewcontent.cgi?article=1623&context=dental_papers&unstamped=1
dc.source.beginpage1487
dc.source.endpage1496
dc.source.issue388
dc.source.issue4
dc.source.journalDepartmental Papers (Dental)
dc.source.journaltitleInfection and Immunity
dc.source.peerreviewedtrue
dc.source.statuspublished
dc.source.volume83
dc.subject.otherDentistry
dc.titleAggregatibacter Actinomycetemcomitans Cytolethal Distending Toxin Activates the NLRP3 Inflammasome in Human Macrophages, Leading to the Release of Proinflammatory Cytokines
dc.typeArticle
digcom.identifierdental_papers/388
digcom.identifier.contextkey31828374
digcom.identifier.submissionpathdental_papers/388
digcom.typearticle
dspace.entity.typePublication
upenn.schoolDepartmentCenterDepartmental Papers (Dental)
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
IAI.03132_14.pdf
Size:
1.27 MB
Format:
Adobe Portable Document Format
Download
Collection
Articles