Maternal allergy and neonatal RSV infection synergize via FcR-mediated allergen uptake to promote the development of asthma in early life.

Summary

Using a population registry and mechanistic mouse models, the study shows that maternal allergy and neonatal RSV synergize to program asthma. Neonatal infection upregulates Fc receptors and cDC2 maturation; maternal allergen-specific IgG transferred via FcRn enhances FcγR-mediated allergen uptake and Th2 priming.

Key Findings

• Registry analysis: infants hospitalized with RSV bronchiolitis born to asthmatic parents had markedly increased subsequent asthma risk.
• Neonatal PVM infection before HDM exposure amplified type 2 inflammation and asthma-like pathology in mice.
• Maternal (not paternal) HDM allergy intensified disease, indicating vertical transmission of an immune risk factor.
• Neonatal viral infection upregulated FcRs and cDC2 maturation; maternal allergen-specific IgG transferred via FcRn enhanced FcγR-mediated allergen uptake and Th2 priming.

Clinical Implications

Supports risk stratification of RSV bronchiolitis in infants born to allergic/asthmatic mothers and motivates maternal/infant-targeted interventions (e.g., maternal immunomodulation, passive antibodies, RSV prevention) to reduce subsequent asthma.

Limitations

• Human registry associations may be confounded despite adjustments; causality primarily supported by animal models.
• Translational applicability to diverse human populations and viruses beyond RSV requires validation.

Future Directions

Test maternal/infant-targeted interventions that modulate FcRn/FcγR pathways or timing of RSV prevention, and validate biomarkers of vertical immune risk in human birth cohorts.