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...

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Bibliographic Details
Published in:PLoS pathogens 2008-02, Vol.4 (2), p.e30
Main Authors: Fang, Min, Lanier, Lewis L, Sigal, Luis J
Format: Article
Language:English
Subjects:
Animals
Cell Line
Cell Survival
Cells
Cytokines - metabolism
Cytotoxicity Tests, Immunologic
Disease Models, Animal
Ectromelia - immunology
Ectromelia - metabolism
Ectromelia virus - immunology
Immune system
Immunity, Cellular
Immunity, Innate - immunology
Immunologic Memory
Immunology
Infections
Infectious Diseases
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Leukocyte Reduction Procedures
Liver - cytology
Local Lymph Node Assay
Lymph Nodes - metabolism
Lymph Nodes - pathology
Mice
Mice, Inbred C57BL
Mus (Mouse)
NK Cell Lectin-Like Receptor Subfamily K
Proteins
Receptors, Immunologic - physiology
Receptors, Natural Killer Cell
Viral infections
Virology
Viruses
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.0040030