State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Disease Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
Department of Hematology, Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Center, Kunming, China.
J Leukoc Biol. 2022 Sep;112(3):499-512. doi: 10.1002/JLB.4A1221-770R. Epub 2022 Apr 18.
Clearance of airway intruders by immune cells is required to resolve infectious pneumonia. However, the molecular mechanisms underlying this process remain elusive. Here, we demonstrated that alveolar macrophage (AM)-derived neuropilin 2 (NRP2) plays an essential role in controlling severe pneumonia by enhancing microbial clearance. Mice with conditional deletion of the NRP2 gene in AM had persistent bacteria, uncontrolled neutrophil influx, and decreased survival during Escherichia coli-induced pneumonia. In vitro assays demonstrated that NRP2 could bind to CD11b Ly6G neutrophils and promote their capacities in phagocytosis and killing of bacteria, which is partially contributed to the increased expression of TLR4 and TNF-a. These findings collectively revealed that AM-derived NRP2 protects the lungs from unwanted injury by promoting the clearance of invading pathogens. This study might provide a promising diagnostic biomarker and therapeutic target for severe pneumonia.
免疫细胞清除气道入侵物是解决传染性肺炎所必需的。然而，这一过程的分子机制仍难以捉摸。在这里，我们证明肺泡巨噬细胞（AM）衍生的神经纤毛蛋白 2（NRP2）通过增强微生物清除作用，在控制严重肺炎方面发挥着重要作用。在 AM 中条件性缺失 NRP2 基因的小鼠在大肠杆菌诱导的肺炎中持续存在细菌，中性粒细胞流入不受控制，存活率降低。体外实验表明，NRP2 可以与 CD11b Ly6G 中性粒细胞结合，并增强其吞噬和杀死细菌的能力，这部分归因于 TLR4 和 TNF-a 的表达增加。这些发现共同揭示了 AM 衍生的 NRP2 通过促进入侵病原体的清除来保护肺部免受不必要的损伤。本研究可能为严重肺炎提供有前途的诊断生物标志物和治疗靶点。
