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IFNs activate toll-like receptor gene expression in viral infections

Genes & Immunity volume 2, pages 349–355 (2001)Cite this article

Abstract

Toll-like receptors (TLRs) mediate innate immune responses to microbes. TLR2, TLR5, TLR6, and TLR9 have been implicated in responses to bacterial components, and TLR4 is the receptor for Gram-negative bacteria. Recently, TLR4 was described to function in respiratory syncytial virus-induced NF-κB activation. Here we have analyzed TLR1–9 mRNA expression in human primary macrophages infected with influenza A and Sendai viruses. TLR1, TLR2, TLR4, TLR6, and TLR8 mRNAs were expressed at basal levels in macrophages. Viral infection enhanced TLR1, TLR2, TLR3, and TLR7 mRNA expression, and neutralizing anti-IFN-α/β antibodies downregulated gene expression of these TLRs. Exogenously added IFN-α upregulated TLR1, TLR2, TLR3, and TLR7 mRNA expression in macrophages, as well as TLR3 mRNA expression in epithelial and endothelial cell lines. IFN-γ enhanced the expression of TLR1 and TLR2 mRNA in macrophages, and TLR3 in epithelial and endothelial cells. The data suggests a novel role for IFNs in the activation of innate immunity.

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Acknowledgements

We thank Mari Aaltonen, Valma Mäkinen, Teija Westerlund, and Marika Yliselä for technical assistance. Drs Osamu Takeuchi and Shizuo Akira are thanked for providing the full-length TLR6 cDNA.

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Authors and Affiliations

  1. Department of Microbiology, National Public Health Institute, Helsinki, Finland

    M Miettinen, T Sareneva, I Julkunen & S Matikainen

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  1. M Miettinen
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  2. T Sareneva
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  3. I Julkunen
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  4. S Matikainen
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Correspondence to M Miettinen.

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This work was supported by the Maud Kuistila Foundation, University of Helsinki 350th Anniversary Fund, the Medical Research Council of the Academy of Finland, the Sigrud Juselius Foundation, the Jenny and Antti Wihuri Foundation, and the Finnish Cancer Foundations.

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Miettinen, M., Sareneva, T., Julkunen, I. et al. IFNs activate toll-like receptor gene expression in viral infections . Genes Immun 2, 349–355 (2001). https://doi.org/10.1038/sj.gene.6363791

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