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Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus

Nature Immunology volume 1, pages 398–401 (2000)Cite this article

Abstract

The innate immune system contributes to the earliest phase of the host defense against foreign organisms and has both soluble and cellular pattern recognition receptors for microbial products. Two important members of this receptor group, CD14 and the Toll-like receptor (TLR) pattern recognition receptors, are essential for the innate immune response to components of Gram-negative and Gram-positive bacteria, mycobacteria, spirochetes and yeast. We now find that these receptors function in an antiviral response as well. The innate immune response to the fusion protein of an important respiratory pathogen of humans, respiratory syncytial virus (RSV), was mediated by TLR4 and CD14. RSV persisted longer in the lungs of infected TLR4-deficient mice compared to normal mice. Thus, a common receptor activation pathway can initiate innate immune responses to both bacterial and viral pathogens.

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Figure 1: Viral proteins stimulate cytokine secretion from PBMC and monocytes.
Figure 2: Cytokine-stimulating activity of RSV F protein is trypsin-sensitive.
Figure 3: Monoclonal antibodies specifically block RSV F cytokine stimulating activity.
Figure 4: CD14 knockout mice do not respond to RSV F protein.
Figure 5: TLR4 is required for macrophage responses to LPS and RSV F protein.
Figure 6: Live RSV persists longer in TLR4-deficient than in control mice.

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Acknowledgements

This work was supported by grants from the National Institutes of Health RO1AI31628 and RO1AI39576 (to R.W.F.), RO1GM54060 and RO1AI38515 (to D.T.G.), and RO1DK50305 (to D.T.G. and M.W.F.).

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Authors and Affiliations

  1. Department of Medicine, University of Massachusetts Medical School, Worcester, 01605, MA, USA

    Evelyn A. Kurt-Jones & Robert W. Finberg

  2. Department of Adult Oncology Dana Farber Cancer Institute and Harvard Medical School, Infectious Disease Program, Boston, 02115, MA, USA

    Evelyn A. Kurt-Jones, Lana Popova, Laura Kwinn & Robert W. Finberg

  3. Division of Viral and Rickettsial Diseases, National Center of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, 30333, GA, USA

    Lia M. Haynes, Les P. Jones, Ralph A. Tripp & Larry J. Anderson

  4. University of Rochester School of Medicine and Dentistry, Rochester, NY, USA

    Edward E. Walsh

  5. Massachusetts General Hospital and Harvard Medical School, Boston, 02115, MA, USA

    Mason W. Freeman

  6. The Maxwell Finland Laboratory for Infectious Diseases, Boston University School of Medicine, Boston, 02118, MA, USA

    Douglas T. Golenbock

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  1. Evelyn A. Kurt-Jones
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Correspondence to Evelyn A. Kurt-Jones.

Supplementary information

Web Figure 1

Lectin purified RSV F protein analyzed by SDS-PAGE under non-reducing conditions. Protein bands were visualized by silver staining. RSV F exists in several naturally occurring forms, including a 145 kD trimer and a 70 kD dimer. F dimers consist of 48 kD and 28 kD components. (MW, molecular weight markers.)

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Kurt-Jones, E., Popova, L., Kwinn, L. et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat Immunol 1, 398–401 (2000). https://doi.org/10.1038/80833

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