2023年12月，重庆医科大学检验医学院检验医学诊断教育部重点实验室，重庆400016;遵义市第一人民医院(遵义医科大学第三附属医院)检验医学科(Key Laboratory of Laboratory Medical Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China；Department of Laboratory Medicine, The First People’s Hospital of Zunyi City (The Third Afliated Hospital of Zunyi Medical University)) Bingyan Wu老师研究团队在《Journal of Translational Medicine》上发表论文：
“The preprogrammed anti-inflammatory phenotypes of CD11chigh macrophages by Streptococcus pneumoniae aminopeptidase N safeguard from allergic asthma”
“肺炎链球菌氨基肽酶N介导CD11c高表达巨噬细胞的预编程抗炎表型保护过敏性哮喘”
Abstract：
Background: Early microbial exposure is associate with protective allergic asthma. We have previously demonstrated that Streptococcus pneumoniae aminopeptidase N (PepN), one of the pneumococcal components, inhibits ovalbumin (OVA) -induced airway inflammation in murine models of allergic asthma, but the underlying mechanism was incompletely determined.
Methods: BALB/c mice were pretreated with the PepN protein and exposed intranasally to HDM allergen. The anti-inflammatory mechanisms were investigated using depletion and adoptive transfer experiments as well as transcriptome analysis and isolated lung CD11chigh macrophages.
Results: We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80+CD11chigh macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11high macrophages. PepN pre-programmed the macrophages during maturation to an anti-inflammatory phenotype by shaping the metabolic preference for oxidative phosphorylation (OXPHOS) and also inhibited the inflammatory response of macrophages by activating AMP-activated protein kinase. Furthermore, PepN treated macrophages also exhibited high-level costimulatory signaling molecules which directed the differentiation into Treg.
Conclusion: Our results demonstrated that the expansion of CD11chigh macrophages in lungs and the OXPHOS metabolic bias of macrophages are associated with reduced allergic airway inflammation after PepN exposure, which paves the way for its application in preventing allergic asthma.
摘要：
背景:早期微生物暴露与保护性过敏性哮喘有关。研究人员之前已经证明肺炎链球菌氨基肽酶N (PepN)是一种肺炎球菌成分，在小鼠过敏性哮喘模型中抑制卵清蛋白(OVA)诱导的气道炎症，但其潜在机制尚不确定。
方法:用PepN蛋白预处理BALB/c小鼠，鼻内暴露HDM变应原。通过耗竭和过继转移实验以及转录组分析和分离的肺cd11高巨噬细胞来研究其抗炎机制。
结果:研究人员发现用PepN预处理小鼠可促进肺内F4/80+ cd11高巨噬细胞的原位增殖，并可动员骨髓单核细胞浸润肺组织，然后转化为cd11高巨噬细胞。PepN通过塑造氧化磷酸化(OXPHOS)的代谢偏好，在巨噬细胞成熟过程中预编程为抗炎表型，并通过激活amp激活的蛋白激酶抑制巨噬细胞的炎症反应。此外，PepN处理的巨噬细胞也表现出高水平的共刺激信号分子，引导分化为Treg。
结论:研究人员的研究结果表明，肺中cd11高的巨噬细胞的扩张和巨噬细胞的OXPHOS代谢偏倚与PepN暴露后过敏性气道炎症的减少有关，这为其在预防过敏性哮喘中的应用奠定了基础。
该论文中，6-8周龄C57BL/6 J小鼠BMDMs（骨髓源性巨噬细胞）的体外培养是使用Ausbian特级胎牛血清完成的。
