DAP12 signaling directly augments proproliferative cytokine stimulation of NK cells during viral infections.
NK cells vigorously proliferate during viral infections. During the course of murine CMV infection, this response becomes dominated by the preferential proliferation of NK cells that express the activation receptor Ly49H. The factors driving such selective NK cell proliferation have not been characterized. In this study, we demonstrate that preferential NK cell proliferation is dependent on DAP12-mediated signaling following the binding of Ly49H to its virally encoded ligand, m157. Ly49H signaling through DAP12 appears to directly augment NK cell sensitivity to low concentrations of proproliferative cytokines such as IL-15. The impact of Ly49H-mediated signaling on NK cell proliferation is masked in the presence of high concentrations of proproliferative cytokines that nonselectively drive all NK cells to proliferate.
French
Anthony R
AR
Division of Pediatric Rheumatology, Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110, USA. french_a@kids.wustl.edu
Sjölin
Hanna
H
Kim
Sungjin
S
Koka
Rima
R
Yang
Liping
L
Young
Deborah A
DA
Cerboni
Cristina
C
Tomasello
Elena
E
Ma
Averil
A
Vivier
Eric
E
Kärre
Klas
K
Yokoyama
Wayne M
WM
D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation; D016207:Cytokines / Q000502:physiology*; D006566:Herpesviridae Infections / Q000276:immunology; D019409:Interleukin-15 / Q000502:physiology; D007694:Killer Cells, Natural / Q000166:cytology / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018146:Muromegalovirus / Q000276:immunology; D055650:NK Cell Lectin-Like Receptor Subfamily A; D018121:Receptors, Cytokine / Q000378:metabolism; D055630:Receptors, NK Cell Lectin-Like; D015398:Signal Transduction; D014777:Virus Diseases / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000950:Antigens, Ly; D016207:Cytokines; D019409:Interleukin-15; C527096:Klra8 protein, mouse; D037181:Lectins, C-Type; D055650:NK Cell Lectin-Like Receptor Subfamily A; D018121:Receptors, Cytokine; D055630:Receptors, NK Cell Lectin-Like; C484963:Tyrobp protein, mouse