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 (T H 2) 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.
Leeuw et al. (2025) studied this question.