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Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands

Nature Immunology volume 10, pages 1200–1207 (2009)Cite this article

A Corrigendum to this article was published on 01 June 2010

This article has been updated

Abstract

Despite the paradigm that the innate immune system uses nucleic acid–specific receptors to detect viruses because of a lack of other conserved features, many viruses are recognized by Toll-like receptor 2 (TLR2) and TLR4. The relevance of this recognition for antiviral immunity remains largely unexplained. Here we report that TLR2 activation by viruses led to the production of type I interferon. TLR2-dependent induction of type I interferon occurred only in response to viral ligands, which indicates that TLR2 is able to discriminate between pathogen classes. We demonstrate that this specialized response was mediated by Ly6Chi inflammatory monocytes. Thus, the innate immune system can detect certain non–nucleic acid features of viruses and links this recognition to the induction of specific antiviral genes.

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Figure 1: TLR2-mediated recognition of vaccinia virus and MCMV.
Figure 2: TLR2 induces the production of type I interferon in response to virus.
Figure 3: Differences in the induction of type I interferon by TLR2 in response to viral and bacterial ligands.
Figure 4: A population of CD11b+CD11c− cells is responsible for TLR2-dependent production of type I interferon.
Figure 5: Ly6Chi IMs produce IFN-β in response to vaccinia virus.
Figure 6: IMs are required for early production of type I interferon and efficient viral clearance in vivo.
Figure 7: TLR2-dependent production of type I interferon requires receptor internalization.

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Change history

  • 12 November 2009

    In the version of this article initially published, the label along the vertical axis of the top row in Figure 6a is incorrect. The correct label should be Ly6G, and the related text in the legend should read “Numbers adjacent to outlined areas indicate Ly6G+CD11b+ cells (top row) or Ly6C+CD11b+ cells (bottom row).” The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank S. Akira (Osaka University) for Myd88−/−Trif−/− mice; D. Portnoy (University of California, Berkeley) for Irf3−/− and Ifnar1−/− mice and ISRE-L929 cells; K. Fitzgerald (University of Massachusetts) for Irf7−/− and Irf3−/−Irf7−/− mice; Z. Chen (University of Texas Southwestern Medical Center) for Mavs−/− mice; D. Raulet (University of California, Berkeley) for vaccinia virus (Western Reserve strain); L. Coscoy (University of California, Berkeley) for MCMV (Smith strain); M. Tokuyama, M. Fontana and K. Camfield for early contributions to this work; M. Mouchess for technical assistance; N. An (Infectious Disease BL2 Core of the Berkeley Center for Host-Pathogen Studies) for help with the production of vaccinia virus; D. Stetson (University of Washington) for key reagents; members of the Barton and Vance labs for discussions and advice; R. Vance and L. Coscoy for comments on the manuscript; and H. Nolla for assistance with flow cytometry. Supported by University of California, the Hellman Family Faculty Fund and the US National Institutes of Health (AI072429 to G.M.B., and GM007232 to R.B.).

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Authors and Affiliations

  1. Division of Immunology and Pathogenesis, Department of Molecular & Cell Biology, University of California, Berkeley, California, USA

    Roman Barbalat, Laura Lau & Gregory M Barton

  2. Department of Medicine and Department of Microbiology & Immunology, Howard Hughes Medical Institute, University of California, San Francisco, California, USA

    Richard M Locksley

Authors
  1. Roman Barbalat
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  2. Laura Lau
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  3. Richard M Locksley
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  4. Gregory M Barton
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Contributions

R.B. and G.M.B. designed the experiments; R.B. and L.L. did the experiments; R.M.L. provided reagents; and R.B. and G.M.B. wrote the manuscript.

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Correspondence to Gregory M Barton.

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Barbalat, R., Lau, L., Locksley, R. et al. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands. Nat Immunol 10, 1200–1207 (2009). https://doi.org/10.1038/ni.1792

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