Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network
Available in PMC 2019 May.
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Association of Immunologists
2020
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| Online Access: | https://hdl.handle.net/1721.1/125549 |
| _version_ | 1826189091550527488 |
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| author | Keegan, Caroline Krutzik, Stephan Schenk, Mirjam Scumpia, Phillip O. 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. Lu, Jing,Ph.D.Massachusetts Institute of Technology. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Keegan, Caroline Krutzik, Stephan Schenk, Mirjam Scumpia, Phillip O. 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. Lu, Jing,Ph.D.Massachusetts Institute of Technology. |
| author_sort | Keegan, Caroline |
| collection | MIT |
| description | Available in PMC 2019 May. |
| first_indexed | 2024-09-23T08:09:43Z |
| format | Article |
| id | mit-1721.1/125549 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:09:43Z |
| publishDate | 2020 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/1255492022-09-23T11:19:40Z Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network Keegan, Caroline Krutzik, Stephan Schenk, Mirjam Scumpia, Phillip O. 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. Lu, Jing,Ph.D.Massachusetts Institute of Technology. Massachusetts Institute of Technology. Department of Biological Engineering Singapore-MIT Alliance in Research and Technology (SMART) Available in PMC 2019 May. Upon 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. National Institutes of Health (U.S.) (NIH Grant R01HL119068) National Institutes of Health (U.S.) (NIH Grant R01AI022553) National Institutes of Health (U.S.) (NIH Grant R01HL129887) National Institutes of Health (U.S.) (NIH Grant R01AR040312) National Institutes of Health (U.S.) (NIH Grant P50AR06302) 2020-05-28T15:31:09Z 2020-05-28T15:31:09Z 2018-05 2019-10-02T12:42:26Z Article http://purl.org/eprint/type/JournalArticle 0022-1767 1550-6606 https://hdl.handle.net/1721.1/125549 Keegan, 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 https://dx.doi.org/10.4049/JIMMUNOL.1701733 Journal of Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association of Immunologists PMC |
| spellingShingle | Keegan, Caroline Krutzik, Stephan Schenk, Mirjam Scumpia, Phillip O. 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. Lu, Jing,Ph.D.Massachusetts Institute of Technology. Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network |
| title | Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network |
| title_full | Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network |
| title_fullStr | Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network |
| title_full_unstemmed | Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network |
| title_short | Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network |
| title_sort | mycobacterium tuberculosis transfer rna induces il 12p70 via synergistic activation of pattern recognition receptors within a cell network |
| url | https://hdl.handle.net/1721.1/125549 |
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