a role for nkg2d in nk cell–mediated resistance to poxvirus diseasenkg2d的角色nk细胞抗痘病毒疾病.pdfVIP

A Role for NKG2D in NK Cell–Mediated Resistance to Poxvirus Disease 1 2,3 1* Min Fang , Lewis L. Lanier , Luis J. Sigal 1 Program of Viral Pathogenesis, Division of Basic Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America, 2 Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, United States of America, 3 Cancer Research Institute, University of California San Francisco, San Francisco, California, United States of America 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. Citation: Fang M, Lanier LL, Sigal LJ (2008) A role for NKG2D in NK cell–mediated resistance to poxvirus disease. PLoS Pathog 4(2): e30. doi:10.1371/journal.ppat.0040030 Introduction dominant gene important for the ability of B6 mice to resist mousepox, maps to the ‘‘NK complex,’’ a region