The adhesion and degranulation-promoting adaptor protein (ADAP) serves as a multifunctional scaffold and is involved in the formation of immune signaling complexes. To date only limited and moreover conflicting data exist regarding the role of ADAP in NK cells. To extend existing knowledge we investigated ADAP-dependency of NK cells in the context of in vivo infection with the intracellular pathogen Listeria monocytogenes (Lm). Ex vivo analysis of infection-primed NK cells revealed impaired cytotoxic capacity in NK cells lacking ADAP as indicated by reduced CD107a surface expression and inefficient perforin production. However, ADAP-deficiency had no global effect on NK cell morphology or intracellular distribution of CD107a-containing vesicles. Proteomic definition of ADAPko and wild type NK cells did not uncover obvious differences in protein composition during the steady state and moreover, similar early response patterns were induced in NK cells upon infection independent of the genotype. In line with protein network analyses that suggested an altered migration phenotype in naïve ADAPko NK cells, in vitro migration assays uncovered significantly reduced migration of both naïve as well as infection-primed ADAPko NK cells compared to wild type NK cells. Notably, this migration defect was associated with a significantly reduced expression of the integrin CD11a on the surface of splenic ADAP-deficient NK cells 1 day post-Lm infection. We propose that ADAP-dependent alterations in integrin expression might account at least in part for the fact that during in vivo infection significantly lower numbers of ADAPko NK cells accumulate in the spleen i.e., the site of infection. In conclusion, we show here that during systemic Lm infection in mice ADAP is essential for efficient cytotoxic capacity and migration of NK cells.

中文翻译：

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ADAP促进小鼠体内单核细胞增生李斯特菌感染期间引发的NK细胞的脱粒和迁移。

粘附和脱粒促进衔接蛋白（ADAP）用作多功能支架，并参与免疫信号复合物的形成。迄今为止，关于ADAP在NK细胞中的作用，仅存在有限且矛盾的数据。为了扩展现有知识，我们在体内感染细胞内病原体单核细胞增生性李斯特菌（Lm）的情况下研究了NK细胞的ADAP依赖性。CD107a表面表达减少和穿孔素生产效率低下表明，感染引发的NK细胞的离体分析显示，缺乏ADAP的NK细胞的细胞毒性能力受损。但是，ADAP缺乏对NK细胞形态或CD107a囊泡的细胞内分布没有全局影响。在稳定状态下，ADAPko和野生型NK细胞的蛋白质组学定义没有发现蛋白质组成上的明显差异，此外，感染后，NK细胞可诱导类似的早期反应模式，而与基因型无关。蛋白质网络分析表明原始的ADAPko NK细胞的迁移表型发生了变化，与野生型NK细胞相比，体外迁移分析发现天然和感染引发的ADAPko NK细胞的迁移均显着降低。值得注意的是，这种迁移缺陷与Lm感染1天后脾ADAP缺陷型NK细胞表面整合素CD11a的表达显着降低有关。我们提出整联蛋白表达中依赖ADAP的改变可能至少部分解释了以下事实：在体内感染期间，脾脏中积累的ADAPko NK细胞数量明显减少，即感染部位。总之，我们在这里表明在小鼠全身性Lm感染过程中，ADAP对于有效的细胞毒性能力和NK细胞迁移至关重要。