PLoS Pathogens | |
Reprogramming of Murine Macrophages through TLR2 Confers Viral Resistance via TRAF3-Mediated, Enhanced Interferon Production | |
Ping Xie1  Meghan E. Pennini2  Darren J. Perkins2  Stefanie N. Vogel2  Swamy K. Polumuri2  Wendy Lai2  | |
[1] Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, United States of America;Department of Microbiology and Immunology, University of Maryland, Baltimore (UMB), School of Medicine, Baltimore, Maryland, United States of America | |
关键词: Macrophages; Toll-like receptors; Interferons; Transcription factors; Vesicular stomatitis virus; Immune receptor signaling; Gene expression; DNA transcription; | |
DOI : 10.1371/journal.ppat.1003479 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
The cell surface/endosomal Toll-like Receptors (TLRs) are instrumental in initiating immune responses to both bacteria and viruses. With the exception of TLR2, all TLRs and cytosolic RIG-I-like receptors (RLRs) with known virus-derived ligands induce type I interferons (IFNs) in macrophages or dendritic cells. Herein, we report that prior ligation of TLR2, an event previously shown to induce “homo” or “hetero” tolerance, strongly “primes” macrophages for increased Type I IFN production in response to subsequent TLR/RLR signaling. This occurs by increasing activation of the transcription factor, IFN Regulatory Factor-3 (IRF-3) that, in turn, leads to enhanced induction of IFN-β, while expression of other pro-inflammatory genes are suppressed (tolerized). In vitro or in vivo “priming” of murine macrophages with TLR2 ligands increase virus-mediated IFN induction and resistance to infection. This priming effect of TLR2 is mediated by the selective upregulation of the K63 ubiquitin ligase, TRAF3. Thus, we provide a mechanistic explanation for the observed antiviral actions of MyD88-dependent TLR2 and further define the role of TRAF3 in viral innate immunity.
【 授权许可】
CC BY
【 预 览 】
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