MyD88 protects from lethal encephalitis during infection with vesicular stomatitis virus

Authors

  • Karl S. Lang,

    Corresponding author
    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
    • Institute of Experimental Immunology, University Hospital, Schmelzbergstrasse 12, 8091 Zurich, Switzerland, Fax: +41-1-255-4420
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    • The first three authors contributed equally to this work.

  • Alexander A. Navarini,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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    • The first three authors contributed equally to this work.

  • Mike Recher,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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    • The first three authors contributed equally to this work.

  • Philipp A. Lang,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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  • Mathias Heikenwalder,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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  • Barbara Stecher,

    1. Institute of Microbiology, ETH Zurich, Zurich, Switzerland
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  • Andreas Bergthaler,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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  • Bernhard Odermatt,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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  • Shizuo Akira,

    1. Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
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  • Kenya Honda,

    1. Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan
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  • Hans Hengartner,

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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  • Rolf M. Zinkernagel

    1. Institutes of Experimental Immunology, Neuropathology and Surgical Pathology, University Hospital of Zurich, Zurich, Switzerland
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Abstract

MyD88 is a key adaptor molecule in innate resistance, engaged in most Toll-like receptor, as well as IL-1 and IL-18, signalling. Here, we analyzed the role of MyD88 in innate resistance during infection with vesicular stomatitis virus (VSV) using myd88–/– mice. We found an increased susceptibility to VSV in myd88–/– mice, which was not explained by reduced type I IFN or neutralizing antibody responses. Susceptibility of myd88–/– mice correlated with impaired recruitment of immune cells to the site of infection. In the absence of MyD88 signalling, VSV rapidly spread to the spinal cord and brain causing lethal encephalitis.

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