DOI: 10.4049/jimmunol.173.12.7416. IFN Regulatory Factor 3-Dependent Induction of Type I IFNs by Intracellular Bacteria Is Mediated by a TLR- and Nod2-Independent Mechanism

IFN Regulatory Factor 3-Dependent Induction of Type I IFNs by Intracellular Bacteria Is Mediated by a TLR- and Nod2-Independent Mechanism
10.4049/jimmunol.173.12.7416
Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract
Abstract Like viruses, intracellular bacteria stimulate their host cells to produce type I IFNs (IFN-α and IFN-β). In our study, we investigated the signals and molecules relevant for the synthesis of and response to IFN by mouse macrophages infected with Listeria monocytogenes. We report that IFN-β is the critical immediate-early IFN made during infection, because the synthesis of all other type I IFN, expression of a subset of infection-induced genes, and the biological response to type I IFN was lost upon IFN-β deficiency. The induction of IFN-β mRNA and the IFN-β-dependent sensitization of macrophages to bacteria-induced death, in turn, was absolutely dependent upon the presence of the transcription factor IFN regulatory factor 3 (IRF3). IFN-β synthesis and signal transduction occurred in macrophages deficient for TLR or their adaptors MyD88, TRIF, or TRAM. Expression of Nod2, a candidate receptor for intracellular bacteria, increased during infection, but the protein was not required for Listeria-induced signal transduction to the Ifn-β gene. Based on our data, we propose that IRF3 is a convergence point for signals derived from structurally unrelated intracellular pathogens, and that L. monocytogenes stimulates a novel TLR- and Nod2-independent pathway to target IRF3 and the type I IFN genes.
Bibliography
Stockinger, S., Reutterer, B., Schaljo, B., Schellack, C., Brunner, S., Materna, T., Yamamoto, M., Akira, S., Taniguchi, T., Murray, P. J., MuÌller, M., & Decker, T. (2004). IFN Regulatory Factor 3-Dependent Induction of Type I IFNs by Intracellular Bacteria Is Mediated by a TLR- and Nod2-Independent Mechanism. The Journal of Immunology, 173(12), 7416â7425.
Authors 12
Silvia Stockinger (first)
Benjamin Reutterer (additional)
Barbara Schaljo (additional)
Carola Schellack (additional)
Sylvia Brunner (additional)
Tilo Materna (additional)
Masahiro Yamamoto (additional)
Shizuo Akira (additional)
Tadatsugu Taniguchi (additional)
Peter J. Murray (additional)
Mathias Müller (additional)
Thomas Decker (additional)
References 76 Referenced 160
Dates
Type	When
Created	11 years, 4 months ago (April 20, 2014, 6:18 p.m.)
Deposited	8 months ago (Jan. 2, 2025, 12:18 p.m.)
Indexed	4 months, 2 weeks ago (April 19, 2025, 12:27 a.m.)
Issued	20 years, 8 months ago (Dec. 15, 2004)
Published	20 years, 8 months ago (Dec. 15, 2004)
Published Print	20 years, 8 months ago (Dec. 15, 2004)
Funders 0
None
BibTeX
@article{Stockinger_2004, title={IFN Regulatory Factor 3-Dependent Induction of Type I IFNs by Intracellular Bacteria Is Mediated by a TLR- and Nod2-Independent Mechanism}, volume={173}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.173.12.7416}, DOI={10.4049/jimmunol.173.12.7416}, number={12}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Stockinger, Silvia and Reutterer, Benjamin and Schaljo, Barbara and Schellack, Carola and Brunner, Sylvia and Materna, Tilo and Yamamoto, Masahiro and Akira, Shizuo and Taniguchi, Tadatsugu and Murray, Peter J. and Müller, Mathias and Decker, Thomas}, year={2004}, month=dec, pages={7416–7425} }
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  "abstract": "<jats:title>Abstract</jats:title>\n               <jats:p>Like viruses, intracellular bacteria stimulate their host cells to produce type I IFNs (IFN-\u03b1 and IFN-\u03b2). In our study, we investigated the signals and molecules relevant for the synthesis of and response to IFN by mouse macrophages infected with Listeria monocytogenes. We report that IFN-\u03b2 is the critical immediate-early IFN made during infection, because the synthesis of all other type I IFN, expression of a subset of infection-induced genes, and the biological response to type I IFN was lost upon IFN-\u03b2 deficiency. The induction of IFN-\u03b2 mRNA and the IFN-\u03b2-dependent sensitization of macrophages to bacteria-induced death, in turn, was absolutely dependent upon the presence of the transcription factor IFN regulatory factor 3 (IRF3). IFN-\u03b2 synthesis and signal transduction occurred in macrophages deficient for TLR or their adaptors MyD88, TRIF, or TRAM. Expression of Nod2, a candidate receptor for intracellular bacteria, increased during infection, but the protein was not required for Listeria-induced signal transduction to the Ifn-\u03b2 gene. Based on our data, we propose that IRF3 is a convergence point for signals derived from structurally unrelated intracellular pathogens, and that L. monocytogenes stimulates a novel TLR- and Nod2-independent pathway to target IRF3 and the type I IFN genes.</jats:p>",
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