Polymicrobial sepsis influences NK-cell-mediated immunity by diminishing NK-cell-intrinsic receptor-mediated effector responses to viral ligands or infections
Fig 6
Sepsis-induces NK-cell-intrinsic functional impairments of Ly49H and Ly49D receptors.
(A) Experimental Design. Splenocytes (day 2 post-surgery) were either incubated with: m157-Tg or WT cells for 6 hrs in the presence of monensin to determine ligand-induced degranulation; with m157 and WT cells for 18 hrs to determine in vitro killing; or 8 hrs stimulation with plate-bound antibody and BFA to determine IFN-γ production. (B) Frequency of CD107a+ Ly49H+ NK-cells in response to ligand (Stim[m157 targets]-Unstim[WT targets]) at indicated effector to target ratios. (C) Number of Ly49H+ NK-cells per well. (D) NK-cell-mediated m157 specific lysis after 18 hrs in vitro incubation. Representative flow plots of IFN-γ (E) or GzmB (F) following stimulation. Frequency of IFN-γ+ (G) or fold GzmB GMFI (H) of stimulated receptor+ NK-cells from Sham or CLP mice after 8 hrs stimulation with plate bound control (IgG), αNK1.1, αNKp46, αLy49D, or αLy49H antibody. Data are representative from 2 independent experiments with 3–5 mice per group. Numbers above bars show fold change between groups. * p<0.05, # p<0.05 group comparison by two-way ANOVA. Error bars represent the standard error of the mean.