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dc.contributor.authorRosowski, Emily Elizabeth
dc.contributor.authorLu, Diana
dc.contributor.authorJulien, Lindsay
dc.contributor.authorRodda, Lauren B.
dc.contributor.authorGaiser, Rogier A.
dc.contributor.authorSaeij, Jeroen
dc.contributor.authorJensen, Kirk D.
dc.date.accessioned2011-08-26T20:12:55Z
dc.date.available2011-08-26T20:12:55Z
dc.date.issued2011-01
dc.date.submitted2010-04
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.urihttp://hdl.handle.net/1721.1/65419
dc.description.abstractNF-κB is an integral component of the immune response to Toxoplasma gondii. Although evidence exists that T. gondii can directly modulate the NF-κB pathway, the parasite-derived effectors involved are unknown. We determined that type II strains of T. gondii activate more NF-κB than type I or type III strains, and using forward genetics we found that this difference is a result of the polymorphic protein GRA15, a novel dense granule protein which T. gondii secretes into the host cell upon invasion. A GRA15-deficient type II strain has a severe defect in both NF-κB nuclear translocation and NF-κB–mediated transcription. Furthermore, human cells expressing type II GRA15 also activate NF-κB, demonstrating that GRA15 alone is sufficient for NF-κB activation. Along with the rhoptry protein ROP16, GRA15 is responsible for a large part of the strain differences in the induction of IL-12 secretion by infected mouse macrophages. In vivo bioluminescent imaging showed that a GRA15-deficient type II strain grows faster compared with wild-type, most likely through its reduced induction of IFN-γ. These results show for the first time that a dense granule protein can modulate host signaling pathways, and dense granule proteins can therefore join rhoptry proteins in T. gondii’s host cell–modifying arsenal.en_US
dc.description.sponsorshipAmerican Heart Association (Scientist Development Grant 0835099N)en_US
dc.description.sponsorshipMassachusetts Life Sciences Centeren_US
dc.description.sponsorshipSingapore. Agency for Science, Technology and Researchen_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (AI080621)en_US
dc.description.sponsorshipCleo and Paul Schimmel Foundationen_US
dc.description.sponsorshipCancer Research Institute (New York, N.Y.)en_US
dc.language.isoen_US
dc.publisherRockefeller University Pressen_US
dc.relation.isversionofhttp://dx.doi.org/10.1084/jem.20100717en_US
dc.rightsCreative Commons Attribution-Non-Commercial-Share Alike 3.0en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/en_US
dc.sourceRockefelleren_US
dc.titleStrain-specific activation of the NF-kappa B pathway by GRA15, a novel Toxoplasma gondii dense granule proteinen_US
dc.typeArticleen_US
dc.identifier.citationRosowski, E. E. et al. “Strain-specific Activation of the NF- B Pathway by GRA15, a Novel Toxoplasma Gondii Dense Granule Protein.” Journal of Experimental Medicine 208.1 (2011) : 195-212.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.approverSaeij, Jeroen
dc.contributor.mitauthorRosowski, Emily Elizabeth
dc.contributor.mitauthorLu, Diana
dc.contributor.mitauthorJulien, Lindsay
dc.contributor.mitauthorRodda, Lauren B.
dc.contributor.mitauthorGaiser, Rogier A.
dc.contributor.mitauthorJensen, Kirk D. C.
dc.contributor.mitauthorSaeij, Jeroen
dc.relation.journalJournal of Experimental Medicineen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsRosowski, E. E.; Lu, D.; Julien, L.; Rodda, L.; Gaiser, R. A.; Jensen, K. D. C.; Saeij, J. P. J.en
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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