Mycobacterium tuberculosis Transfer RNA Induces IL-12p70 via Synergistic Activation of Pattern Recognition Receptors within a Cell Network
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nihms950135.pdf
Description
Accepted version
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3.03 MB
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Author(s)
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
Date Issued
May 2018
Journal
Journal of Immunology
Publisher
American Association of Immunologists
Citation
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.
Version
Author's final manuscript
Abstract
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.
Description
Available in PMC 2019 May.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Singapore-MIT Alliance in Research and Technology (SMART)
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.4049/JIMMUNOL.1701733
