Role of MyD88 in route-dependent susceptibility to vesicular stomatitis virus infection.
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-alpha 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.
Zhou
Shenghua
S
Department of Medicine, University of Massachusetts Medical Center, Worcester, MA 01605, USA.
Kurt-Jones
Evelyn A
EA
Fitzgerald
Katherine A
KA
Wang
Jennifer P
JP
Cerny
Anna M
AM
Chan
Melvin
M
Finberg
Robert W
RW
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004198:Disease Susceptibility; D016898:Interferon-alpha / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis; D007375:Interleukin-1 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D018353:Rhabdoviridae Infections / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology
D000914:Antibodies, Viral; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016898:Interferon-alpha; D007375:Interleukin-1; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D007371:Interferon-gamma