母体过敏与新生儿呼吸道合胞病毒感染通过Fc受体介导的过敏原摄取协同促进生命早期哮喘发生
2025/12/30
摘要
过敏性哮喘的发生源于复杂的遗传与环境相互作用。基于大规模人群登记系统的分析发现，父母患有哮喘的婴儿若因呼吸道合胞病毒（RSV）细支气管炎住院，其日后发生哮喘的风险显著增加。为模拟这一相互作用，在暴露于屋尘螨（HDM）前感染小鼠肺炎病毒（PVM，RSV类似物）的新生小鼠表现出加重的2型炎症反应及哮喘样病理改变。母源（而非父源）HDM过敏会加剧疾病进程，提示存在免疫风险因素的垂直传递。机制研究表明，新生儿期病毒感染上调了Fc受体表达，并促进2型经典树突状细胞成熟。经新生儿Fc受体转运的母源过敏原特异性免疫球蛋白G，通过增强Fcγ受体介导的过敏原摄取及辅助性T细胞2亚群的活化，驱动疾病发展。在此模型中，预防性RSV免疫预防可阻断哮喘发生。这些发现明确了母体过敏与新生儿RSV感染是通过Fc受体依赖机制协同作用的哮喘致病风险因素，且可通过免疫预防进行干预。
Maternal allergy and neonatal RSV infection synergize via FcR-mediated allergen uptake to promote the development of asthma in early life.
Elisabeth, De Leeuw; Josefine F,
Allergic asthma arises from complex genetic and environmental interactions. Analysis of a population-wide registry revealed that infants hospitalized for human respiratory syncytial virus (RSV) bronchiolitis who are born to asthmatic parents have a markedly increased risk of developing asthma. To model this interaction, neonatal mice infected with pneumonia virus of mice (PVM), an RSV analog, before house dust mite (HDM) exposure developed amplified type 2 inflammation and asthma-like pathology. Maternal, but not paternal, HDM allergy intensified disease, implicating vertical transmission of an immune risk factor. Mechanistically, neonatal viral infection up-regulated Fc receptors (FcRs) and promoted maturation of type 2 conventional dendritic cells (cDC2s). Maternal allergen-specific immunoglobulin G (IgG), transferred via neonatal Fc receptor (FcRn), enhanced Fc gamma receptor (FcγR)-mediated allergen uptake and T helper 2 (TH2) cell priming. Preventive RSV immunoprophylaxis blocked asthma development in this setting. These findings identify maternal allergy and neonatal RSV infection as converging FcR-dependent causal asthma risk factors, preventable through immunoprophylaxis.
过敏性哮喘的发生源于复杂的遗传与环境相互作用。基于大规模人群登记系统的分析发现，父母患有哮喘的婴儿若因呼吸道合胞病毒（RSV）细支气管炎住院，其日后发生哮喘的风险显著增加。为模拟这一相互作用，在暴露于屋尘螨（HDM）前感染小鼠肺炎病毒（PVM，RSV类似物）的新生小鼠表现出加重的2型炎症反应及哮喘样病理改变。母源（而非父源）HDM过敏会加剧疾病进程，提示存在免疫风险因素的垂直传递。机制研究表明，新生儿期病毒感染上调了Fc受体表达，并促进2型经典树突状细胞成熟。经新生儿Fc受体转运的母源过敏原特异性免疫球蛋白G，通过增强Fcγ受体介导的过敏原摄取及辅助性T细胞2亚群的活化，驱动疾病发展。在此模型中，预防性RSV免疫预防可阻断哮喘发生。这些发现明确了母体过敏与新生儿RSV感染是通过Fc受体依赖机制协同作用的哮喘致病风险因素，且可通过免疫预防进行干预。
（中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校）
（Sci Immunol 2025 Nov 28;10(113):eadz4626 DOI:10.1126/sciimmunol.adz4626 IF: 13.44）
（Sci Immunol 2025 Nov 28;10(113):eadz4626 DOI:10.1126/sciimmunol.adz4626 IF: 13.44）
Maternal allergy and neonatal RSV infection synergize via FcR-mediated allergen uptake to promote the development of asthma in early life.
Elisabeth, De Leeuw; Josefine F,
Allergic asthma arises from complex genetic and environmental interactions. Analysis of a population-wide registry revealed that infants hospitalized for human respiratory syncytial virus (RSV) bronchiolitis who are born to asthmatic parents have a markedly increased risk of developing asthma. To model this interaction, neonatal mice infected with pneumonia virus of mice (PVM), an RSV analog, before house dust mite (HDM) exposure developed amplified type 2 inflammation and asthma-like pathology. Maternal, but not paternal, HDM allergy intensified disease, implicating vertical transmission of an immune risk factor. Mechanistically, neonatal viral infection up-regulated Fc receptors (FcRs) and promoted maturation of type 2 conventional dendritic cells (cDC2s). Maternal allergen-specific immunoglobulin G (IgG), transferred via neonatal Fc receptor (FcRn), enhanced Fc gamma receptor (FcγR)-mediated allergen uptake and T helper 2 (TH2) cell priming. Preventive RSV immunoprophylaxis blocked asthma development in this setting. These findings identify maternal allergy and neonatal RSV infection as converging FcR-dependent causal asthma risk factors, preventable through immunoprophylaxis.
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