Maternal allergy and neonatal RSV infection synergize via FcR-mediated allergen uptake to promote the development of asthma in early life
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<sub>H</sub>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.
Authors
- Cédric Bosteels (ORCID: https://orcid.org/0000-0003-3230-0879)
- Elisabeth De Leeuw (ORCID: https://orcid.org/0000-0002-7826-8141)
- Hamida Hammad (ORCID: https://orcid.org/0000-0003-3762-8603)
- Nincy Debeuf (ORCID: https://orcid.org/0000-0002-4754-4772)
- Karel Van Damme (ORCID: https://orcid.org/0000-0002-4379-1047)
- Stijn Vanhee (ORCID: https://orcid.org/0000-0001-5305-1651)
- Sam Dupont (ORCID: https://orcid.org/0000-0002-7020-5373)
- Manon Vanheerswynghels (ORCID: https://orcid.org/0000-0001-9082-2267)
- Morten Dahl (ORCID: https://orcid.org/0000-0002-6686-312X)
- Leander Jonckheere (ORCID: https://orcid.org/0000-0003-1606-495X)
- Caroline De Wolf (ORCID: https://orcid.org/0009-0008-0549-2215)
- Just Justesen (ORCID: https://orcid.org/0000-0002-5746-0839)
- Bart N. Lambrecht (ORCID: https://orcid.org/0000-0003-4376-6834)
- Kim Deswarte (ORCID: https://orcid.org/0000-0002-9761-6973)
- Manon Lesage
- Alysia Wayenberg (ORCID: https://orcid.org/0009-0005-6835-7000)
Institutions
- University of Copenhagen (DK)
- Ghent University Hospital (BE)
- Erasmus MC (NL)
- Ghent University (BE)
- VIB-UGent Center for Inflammation Research (BE)
- Zealand University Hospital Køge (DK)
- Argenx (Belgium) (BE)
- Erasmus University Rotterdam (NL)
Publication Details
- Journal
- Science Immunology
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1126/sciimmunol.adz4626
- Citations
- 3
- Primary Topic
- Respiratory viral infections research
- Type
- article
- Field-Weighted Citation Impact
- 4.06