A role for NKG2D in NK cell-mediated resistance to poxvirus disease.
Ectromelia virus (ECTV) is an orthopoxvirus (OPV) that causes mousepox, the murine equivalent of human smallpox. C57BL/6 (B6) mice are naturally resistant to mousepox due to the concerted action of innate and adaptive immune responses. Previous studies have shown that natural killer (NK) cells are a component of innate immunity that is essential for the B6 mice resistance to mousepox. However, the mechanism of NK cell-mediated resistance to OPV disease remains undefined. Here we show that B6 mice resistance to mousepox requires the direct cytolytic function of NK cells, as well as their ability to boost the T cell response. Furthermore, we show that the activating receptor NKG2D is required for optimal NK cell-mediated resistance to disease and lethality. Together, our results have important implication towards the understanding of natural resistance to pathogenic viral infections.
Fang
Min
M
Program of Viral Pathogenesis, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.
Lanier
Lewis L
LL
Sigal
Luis J
LJ
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003601:Cytotoxicity Tests, Immunologic; D004195:Disease Models, Animal; D004480:Ectromelia / Q000276:immunology* / Q000378:metabolism; D004481:Ectromelia virus / Q000276:immunology*; D007111:Immunity, Cellular; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D047589:Leukocyte Reduction Procedures; D008099:Liver / Q000166:cytology; D023441:Local Lymph Node Assay; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000502:physiology*; D055607:Receptors, Natural Killer Cell
D016207:Cytokines; C527085:KLRK1 protein, human; C527086:Klrk1 protein, mouse; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell