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Role of MyD88 in Route-Dependent Susceptibility to Vesicular Stomatitis Virus Infection¹

Department of Medicine, University of Massachusetts Medical Center, Worcester, MA 01605

TLRs are important components of the innate immune response. The role of the TLR signaling pathway in host defense against a natural viral infection has been largely unexplored. We found that mice lacking MyD88, an essential adaptor protein in TLR signaling pathway, were extremely sensitive to intranasal infection with vesicular stomatitis virus, and this susceptibility was dose dependent. We demonstrated that this increased susceptibility correlates with the impaired production of IFN- and defective induction and maintenance of neutralizing Ab. These studies outline the important role of the TLR signaling pathway in nasal mucosae-respiratory tracts-neuroepithelium environment in the protection against microbial pathogen infections. We believe that these results explain how the route of infection, probably by virtue of activating different cell populations, can lead to entirely different outcomes of infection based on the underlying genetics of the host.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institute of Allergy and Infectious Diseases Regional Center of Excellence Grant AI 057159 and National Institutes of Health Grants R01 AI 49309 (to R.W.F.) and P01 AI 0577484.

² Address correspondence and reprint requests to Dr. Robert W. Finberg, Department of Medicine, University of Massachusetts Medical Center, 364 Plantation Street, Lazare Research Building, Worcester, MA 01605. E-mail address: Robert.Finberg{at}umassmed.edu

³ Abbreviations used in this paper: VSV, vesicular stomatitis virus; DC, dendritic cell; pDC, plasmacytoid DC; Flt3L, human recombinant fms-related tyrosine kinase 3 ligand; KO, knockout; WT, wild type.

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