The preprogrammed anti-inflammatory phenotypes of CD11c<SUP>high</SUP> macrophages by <i>Streptococcus pneumoniae</i> aminopeptidase N safeguard from allergic asthma

作者全名："Yao, Shifei; Weng, Danlin; Wang, Yan; Zhang, Yanyu; Huang, Qi; Wu, Kaifeng; Li, Honghui; Zhang, Xuemei; Yin, Yibing; Xu, Wenchun"

作者地址："[Yao, Shifei; Weng, Danlin; Wang, Yan; Zhang, Yanyu; Huang, Qi; Li, Honghui; Zhang, Xuemei; Yin, Yibing; Xu, Wenchun] Chongqing Med Univ, Sch Lab Med, Key Lab Diagnost Med Designated, Minist Educ, Chongqing 400016, Peoples R China; [Yao, Shifei; Wu, Kaifeng] Zunyi Med Univ, Peoples Hosp Zunyi City 1, Affiliated Hosp 3, Dept Lab Med, Zunyi 563000, Peoples R China"

通信作者："Xu, WC (通讯作者)，Chongqing Med Univ, Sch Lab Med, Key Lab Diagnost Med Designated, Minist Educ, Chongqing 400016, Peoples R China."

来源：JOURNAL OF TRANSLATIONAL MEDICINE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001123747000003

JCR分区：Q1

影响因子：6.1

年份：2023

卷号：21

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Hygiene hypothesis; Allergic asthma; Streptococcus pneumoniae aminopeptidase N; Macrophage; Oxidation phosphorylation

摘要："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 CD11c(high) macrophages.Results We found pretreatment of mice with PepN promoted the proliferation of lung-resident F4/80(+)CD11c(high) macrophages in situ but also mobilized bone marrow monocytes to infiltrate lung tissue that were then transformed into CD11(high) 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 CD11c(high) 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."

基金机构：National Natural Science Foundation of China; Children's Hospital of Chongqing Medical University; Ministry of Education Key Laboratory of Development and Disorders at Children's Hospital of Chongqing Medical University

基金资助正文：We thank Prof. Xiaodong Zhao from Children's Hospital of Chongqing Medical University for providing the CD45.1 mice for bone marrow chimera experiments. We are grateful to the Flow Cytometry and Informatic and Data Analysis Core facilities from Ministry of Education Key Laboratory of Development and Disorders at Children's Hospital of Chongqing Medical University.