The ITIM Domain–Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions
The ITIM Domain–Containing NK Receptor Ly49Q Impacts Pulmonary Infection by Mediating Neutrophil Functions
复制标题
DOI：
10.4049/jimmunol.1701084
复制
发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
A. Margraf;Stephanie Volmering;Jennifer Skupski;V. van Marck;A. Makrigiannis;H. Block;A. Zarbock
中科院分区：
文献类型：
--
作者：
A. Margraf;Stephanie Volmering;Jennifer Skupski;V. van Marck;A. Makrigiannis;H. Block;A. Zarbock
肺部感染是一种常见的病理与过度中性粒细胞浸润。Ly 49 Q是一种在不同白细胞上表达的具有ITIM结构域的受体，最近已报道其影响中性粒细胞迁移和极化。利用小鼠肺炎克雷伯氏菌诱导的肺部感染模型，结合额外的体内和体外试验，我们表明，Ly 49 Q是关键参与白细胞粘附级联反应的不同步骤。Ly 49 Q缺乏与滚动速度降低、爬行能力受损和迁移减少有关。我们发现，中性粒细胞β2整合素Mac-1和LFA-1的过度活化是导致粘附增加和中性粒细胞迁移减少的原因，导致对肺部感染的免疫防御严重受损。体内外结构功能分析表明Ly 49 Q的不同结构域对其功能有重要作用。总之，Ly 49 Q调节整合素活化和中性粒细胞募集，并且是肺部感染中充分免疫应答所需的。
Pulmonary infection is a frequent pathology associated with excessive neutrophil infiltration. Ly49Q, an ITIM domain–bearing receptor expressed on different leukocytes, has been recently reported to impact neutrophil migration and polarization. Utilizing a murine model of Klebsiella pneumoniae–induced pulmonary infection in combination with additional in vivo and in vitro assays, we show that Ly49Q is critically involved in different steps of the leukocyte adhesion cascade. Ly49Q deficiency is associated with a reduced rolling velocity, impaired crawling capacity, and diminished transmigration. We show that overactivation of the neutrophil β2 integrins Mac-1 and LFA-1 is responsible for increased adhesion and reduced neutrophil transmigration, resulting in a strongly impaired immune defense against pulmonary infection. Structure function analysis in vitro and in vivo demonstrated that different domains of Ly49Q are important for its function. In summary, Ly49Q regulates integrin activation and neutrophil recruitment and is required for an adequate immune response in pulmonary infection.