Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection
Open Access
- 30 March 2009
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 206 (4), 807-817
- https://doi.org/10.1084/jem.20090168
Abstract
The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H+ NK cells, expressing only Ly49H–DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-γ upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell–mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12.This publication has 57 references indexed in Scilit:
- Adaptive immune features of natural killer cellsNature, 2009
- DAP10‐ and DAP12‐associated receptors in innate immunityImmunological Reviews, 2008
- Up on the tightrope: natural killer cell activation and inhibitionNature Immunology, 2008
- Evolutionary struggles between NK cells and virusesNature Reviews Immunology, 2008
- DAP12: an adapter protein with dual functionalityImmunological Reviews, 2006
- The herpesviral Fc receptor fcr-1 down-regulates the NKG2D ligands MULT-1 and H60The Journal of Experimental Medicine, 2006
- Dysregulation of signaling pathways in CD45-deficient NK cells leads to differentially regulated cytotoxicity and cytokine productionProceedings of the National Academy of Sciences of the United States of America, 2006
- The DNA damage pathway regulates innate immune system ligands of the NKG2D receptorNature, 2005
- Activation of NK Cells and T Cells by NKG2D, a Receptor for Stress-Inducible MICAScience, 1999
- Severe Herpesvirus Infections in an Adolescent without Natural Killer CellsThe New England Journal of Medicine, 1989