RT Journal Article SR Electronic T1 Role of MyD88 in Route-Dependent Susceptibility to Vesicular Stomatitis Virus Infection JF The Journal of Immunology JO J. Immunol. FD American Association of Immunologists SP 5173 OP 5181 DO 10.4049/jimmunol.178.8.5173 VO 178 IS 8 A1 Zhou, Shenghua A1 Kurt-Jones, Evelyn A. A1 Fitzgerald, Katherine A. A1 Wang, Jennifer P. A1 Cerny, Anna M. A1 Chan, Melvin A1 Finberg, Robert W. YR 2007 UL http://www.jimmunol.org/content/178/8/5173.abstract AB 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-α 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.