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dc.contributor.authorKeegan, Caroline
dc.contributor.authorKrutzik, Stephan
dc.contributor.authorSchenk, Mirjam
dc.contributor.authorScumpia, Phillip O.
dc.contributor.authorLu, Jing
dc.contributor.authorPang, Yan Ling Joy
dc.contributor.authorRussell, Brandon S
dc.contributor.authorLim, Kok Seong
dc.contributor.authorShell, Scarlet
dc.contributor.authorPrestwich, Erin
dc.contributor.authorSu, Dan
dc.contributor.authorElashoff, David
dc.contributor.authorHershberg, Robert M.
dc.contributor.authorBloom, Barry R.
dc.contributor.authorBelisle, John T.
dc.contributor.authorFortune, Sarah
dc.contributor.authorDedon, Peter C
dc.contributor.authorPellegrini, Matteo
dc.contributor.authorModlin, Robert L.
dc.date.accessioned2020-05-28T15:31:09Z
dc.date.available2020-05-28T15:31:09Z
dc.date.issued2018-05
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.urihttps://hdl.handle.net/1721.1/125549
dc.descriptionAvailable in PMC 2019 May.en_US
dc.description.abstractUpon recognition of a microbial pathogen, the innate and adaptive immune systems are linked to generate a cell-mediated immune response against the foreign invader. The culture filtrate of Mycobacterium tuberculosis contains ligands, such as M. tuberculosis tRNA, that activate the innate immune response and secreted Ags recognized by T cells to drive adaptive immune responses. In this study, bioinformatics analysis of gene-expression profiles derived from human PBMCs treated with distinct microbial ligands identified a mycobacterial tRNA-induced innate immune network resulting in the robust production of IL-12p70, a cytokine required to instruct an adaptive Th1 response for host defense against intracellular bacteria. As validated by functional studies, this pathway contained a feed-forward loop, whereby the early production of IL-18, type I IFNs, and IL-12p70 primed NK cells to respond to IL-18 and produce IFN-g, enhancing further production of IL-12p70. Mechanistically, tRNA activates TLR3 and TLR8, and this synergistic induction of IL-12p70 was recapitulated by the addition of a specific TLR8 agonist with a TLR3 ligand to PBMCs. These data indicate that M. tuberculosis tRNA activates a gene network involving the integration of multiple innate signals, including types I and II IFNs, as well as distinct cell types to induce IL-12p70. The Journal of Immunology, 2018, 200: 3244–3258.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant R01HL119068)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant R01AI022553)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant R01HL129887)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant R01AR040312)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Grant P50AR06302)en_US
dc.language.isoen
dc.publisherAmerican Association of Immunologistsen_US
dc.relation.isversionofhttps://dx.doi.org/10.4049/JIMMUNOL.1701733en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleMycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Networken_US
dc.typeArticleen_US
dc.identifier.citationKeegan, Caroline, et al. "Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network." The Journal of Immunology. 2018, May 01; 200(9): 3244–3258. Copyright © 2018 by The American Association of Immunologists, Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.departmentSingapore-MIT Alliance in Research and Technology (SMART)en_US
dc.relation.journalJournal of Immunologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2019-10-02T12:42:26Z
dspace.orderedauthorsKeegan, Caroline; Krutzik, Stephan; Schenk, Mirjam; Scumpia, Phillip O.; Lu, Jing; Pang, Yan Ling Joy; Russell, Brandon S.; Lim, Kok Seong; Shell, Scarlet; Prestwich, Erin; Su, Dan; Elashoff, David; Hershberg, Robert M.; Bloom, Barry R.; Belisle, John T.; Fortune, Sarah; Dedon, Peter C.; Pellegrini, Matteo; Modlin, Robert L.en_US
dspace.date.submission2019-10-02T12:42:30Z
mit.journal.volume200en_US
mit.journal.issue9en_US


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