Lydia Becker Institute for Immunology and Inflammation, Manchester, UK.
Wellcome Trust Centre for Cell-Matrix Research, Manchester, UK.
Nat Commun. 2019 May 9;10(1):2121. doi: 10.1038/s41467-019-10156-6.
Pulmonary immune control is crucial for protection against pathogens. Here we identify a pathway that promotes host responses during pulmonary bacterial infection; the expression of CD200 receptor (CD200R), which is known to dampen pulmonary immune responses, promotes effective clearance of the lethal intracellular bacterium Francisella tularensis. We show that depletion of CD200R in mice increases in vitro and in vivo infectious burden. In vivo, CD200R deficiency leads to enhanced bacterial burden in neutrophils, suggesting CD200R normally limits the neutrophil niche for infection. Indeed, depletion of this neutrophil niche in CD200R mice restores F. tularensis infection to levels seen in wild-type mice. Mechanistically, CD200R-deficient neutrophils display significantly reduced reactive oxygen species production (ROS), suggesting that CD200R-mediated ROS production in neutrophils is necessary for limiting F. tularensis colonisation and proliferation. Overall, our data show that CD200R promotes the antimicrobial properties of neutrophils and may represent a novel antibacterial therapeutic target.
肺部的免疫控制对于防止病原体感染至关重要。在这里，我们发现了一条促进宿主对肺部细菌感染产生反应的途径；CD200 受体（CD200R）的表达，已知会抑制肺部免疫反应，促进对致命的细胞内细菌弗朗西斯菌的有效清除。我们表明，在小鼠中耗尽 CD200R 会增加体外和体内的感染负担。在体内，CD200R 缺乏会导致中性粒细胞中的细菌负担增加，这表明 CD200R 通常限制了感染中性粒细胞的生态位。事实上，耗尽 CD200R 小鼠的这种中性粒细胞生态位可将弗氏柠檬酸杆菌的感染恢复到野生型小鼠的水平。从机制上讲，缺乏 CD200R 的中性粒细胞显示出明显减少的活性氧（ROS）产生，这表明 CD200R 介导的中性粒细胞中 ROS 的产生对于限制弗氏柠檬酸杆菌的定植和增殖是必要的。总体而言，我们的数据表明 CD200R 促进了中性粒细胞的抗菌特性，可能代表一种新的抗菌治疗靶点。
