经局部调节的CXCR4hi中性粒细胞通过释放中性粒细胞胞外杀菌网络触发环境驱动的过敏性哮喘
2019/11/12
摘要
低微生物产物暴露、呼吸道病毒感染和空气污染是过敏性哮喘的主要危险因素，但这种情况与宿主对2型过敏性疾病的易感性之间的机制联系仍不清楚。通过使用单细胞RNA测序，我们描述了先经过低剂量的脂多糖（LPS）或保护性高剂量的LPS暴露再经屋尘螨暴露的小鼠肺中性粒细胞的特征。与暴露于高剂量的LPS不同，暴露于低剂量的LPS指引募集的中性粒细胞上调其趋化因子受体CXCR4的表达并释放中性粒细胞胞外杀菌网络。低剂量LPS诱导的中性粒细胞和中性粒细胞胞外杀菌网络可增强CD11b+Ly-6C+树突状细胞对屋尘螨的摄取，并增强房尘螨诱发的2型变应性气道炎症。流感病毒感染或暴露于臭氧引发的过敏性哮喘同样需要CXCR4hi中性粒细胞来源的中性粒细胞胞外杀菌网络来介导。我们的研究表明，那些看起来不相关的环境危险因素可以重塑肺部募集的中性粒细胞，从而促进诱发过敏性哮喘。
Locally instructed CXCR4hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps.
Radermecker C, Sabatel C, Vanwinge C, Ruscitti C, Maréchal P, Perin F, Schyns J, Rocks N, Toussaint M, Cataldo D, Johnston SL, Bureau F, Marichal T.
Abstract
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b+Ly-6C+ dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4hi neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.
低微生物产物暴露、呼吸道病毒感染和空气污染是过敏性哮喘的主要危险因素，但这种情况与宿主对2型过敏性疾病的易感性之间的机制联系仍不清楚。通过使用单细胞RNA测序，我们描述了先经过低剂量的脂多糖（LPS）或保护性高剂量的LPS暴露再经屋尘螨暴露的小鼠肺中性粒细胞的特征。与暴露于高剂量的LPS不同，暴露于低剂量的LPS指引募集的中性粒细胞上调其趋化因子受体CXCR4的表达并释放中性粒细胞胞外杀菌网络。低剂量LPS诱导的中性粒细胞和中性粒细胞胞外杀菌网络可增强CD11b+Ly-6C+树突状细胞对屋尘螨的摄取，并增强房尘螨诱发的2型变应性气道炎症。流感病毒感染或暴露于臭氧引发的过敏性哮喘同样需要CXCR4hi中性粒细胞来源的中性粒细胞胞外杀菌网络来介导。我们的研究表明，那些看起来不相关的环境危险因素可以重塑肺部募集的中性粒细胞，从而促进诱发过敏性哮喘。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Nat Immunol. 2019 Oct 7. doi: 10.1038/s41590-019-0496-9.)
(Nat Immunol. 2019 Oct 7. doi: 10.1038/s41590-019-0496-9.)
Locally instructed CXCR4hi neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps.
Radermecker C, Sabatel C, Vanwinge C, Ruscitti C, Maréchal P, Perin F, Schyns J, Rocks N, Toussaint M, Cataldo D, Johnston SL, Bureau F, Marichal T.
Abstract
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS-induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b+Ly-6C+ dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4hi neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.
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