S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis
The mechanism of the association of S. aureus skin colonization with food allergy in atopic dermatitis (AD) is unknown. Interleukin-4 (IL-4) plays an important role in food allergy. We found elevated serum IL-4 concentrations in AD patients with S. aureus skin colonization and food allergy. Using an AD mouse model, we demonstrated that epicutaneous application of antigen together with superantigen-producing S. aureus, or staphylococcal enterotoxin B (SEB), caused a heightened systemic antigen-specific T helper-2 (Th2) response and elevated serum IL-4 concentrations. T cell-derived IL-4 acted on intestinal epithelial cells to enhance intestinal permeability and anaphylaxis to enteral antigen challenge. CD40-dependent SEB binding to keratinocytes triggered IL-33 release, which caused T cells to produce IL-3 that elicited a basophil influx in skin-draining lymph nodes (dLNs). Basophil-derived IL-4 augmented Th2 cell polarization by antigen-bearing dendritic cells from skin dLNs. These results suggest therapeutic interventions that might attenuate food allergy in AD patients.
Authors
- Robert M. Anthony (ORCID: https://orcid.org/0000-0002-7283-7825)
- Elena Goleva (ORCID: https://orcid.org/0000-0002-4685-9318)
- Donald Y.M. Leung (ORCID: https://orcid.org/0000-0002-0177-3844)
- Megan Elkins
- Simon P. Hogan (ORCID: https://orcid.org/0000-0001-5793-4304)
- Janet Chou (ORCID: https://orcid.org/0000-0002-4610-2657)
- Fred D. Finkelman (ORCID: https://orcid.org/0000-0002-1815-1902)
- Kenneth M. Murphy (ORCID: https://orcid.org/0000-0002-3505-9630)
- Hans C. Oettgen (ORCID: https://orcid.org/0000-0003-1199-1391)
- Shabnam Abtahi (ORCID: https://orcid.org/0000-0003-3096-8023)
- Wanda Phipatanakul (ORCID: https://orcid.org/0000-0001-8639-0473)
- Raif S. Geha (ORCID: https://orcid.org/0000-0002-6019-3751)
- Frank Brombacher (ORCID: https://orcid.org/0000-0001-8881-6781)
- Brian Woods (ORCID: https://orcid.org/0000-0003-4363-4444)
- Maheshwor Timilshina
- Jerrold R. Turner
- Jacqueline Ngo
- Patrick M. Schlievert (ORCID: https://orcid.org/0000-0001-8314-9369)
- Mohammed Alasharee
- Mei Li (ORCID: https://orcid.org/0000-0003-4225-6699)
- Sohee Kim (ORCID: https://orcid.org/0000-0001-5070-002X)
- Mrinmoy Das (ORCID: https://orcid.org/0000-0002-9932-9548)
- George F. Murphy (ORCID: https://orcid.org/0000-0002-3909-1160)
- Saikat Mukherjee (ORCID: https://orcid.org/0000-0002-4330-8588)
- Juan Manuel Leyva-Castillo (ORCID: https://orcid.org/0000-0001-7394-4457)
- Ana Flávia Santarine Laureano
- Shannon M. McNamee
- Logan Magin
Institutions
- Université Claude Bernard Lyon 1 (FR)
- University of Iowa (US)
- Brigham and Women's Hospital (US)
- Cincinnati Children's Hospital Medical Center (US)
- Boston Children's Hospital (US)
- Centre National de la Recherche Scientifique (FR)
- Harvard University (US)
- SRM Institute of Science and Technology (IN)
- University of Cape Town (ZA)
- Washington University in St. Louis (US)
- University of Michigan (US)
- National Jewish Health (US)
- Institut de génétique et de biologie moléculaire et cellulaire (FR)
- Massachusetts General Hospital (US)
- Centre de Recherche des Cordeliers (FR)
- Institut Lumière Matière (FR)
- Usha Martin (India) (IN)
- Université de Strasbourg (FR)
- University of Cincinnati Medical Center (US)
- University of Colorado Denver (US)
Publication Details
- Journal
- Immunity
- Published
- 2025-09-25
- DOI
- https://doi.org/10.1016/j.immuni.2025.09.001
- Citations
- 4
- Primary Topic
- Food Allergy and Anaphylaxis Research
- Type
- article
- Field-Weighted Citation Impact
- 6.49
Funders
- Agence Nationale de la Recherche
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases