S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis

Mrinmoy Das; Mohammed Alasharee; Brian Woods; Saikat Mukherjee; Shira Kim; Megan Elkins; Jacqueline Ngo; Logan Magin; Maheshwor Timilshina; Juan Manuel Leyva-Castillo; Kenneth M. Murphy; Robert M. Anthony; Ana Flávia Santarine Laureano; George F. Murphy; Shannon McNamee; Frank Brombacher; Simon P. Hogan; Jerrold R. Turner; Shabnam Abtahi; Wanda Phipatanakul; Donald Y.M. Leung; Elena Goleva; Hans C. Oettgen; Mei Li; Janet Chou; Patrick M. Schlievert; Fred D. Finkelman; Raif S. Geha

doi:10.1016/j.immuni.2025.09.001

S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis

Mrinmoy Das
, Mohammed Alasharee
, Brian Woods
, Saikat Mukherjee
, Shira Kim
, Megan Elkins
, Jacqueline Ngo
, Logan Magin
, Maheshwor Timilshina
, Juan Manuel Leyva-Castillo
, Kenneth M. Murphy
, Robert M. Anthony
, Ana Flávia Santarine Laureano
, George F. Murphy
, Shannon McNamee
, Frank Brombacher
, Simon P. Hogan
, Jerrold R. Turner
, Shabnam Abtahi
, Wanda Phipatanakul

Donald Y.M. Leung, Elena Goleva, Hans C. Oettgen, Mei Li, Janet Chou, Patrick M. Schlievert, Fred D. Finkelman, Raif S. Geha

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	2769-2784.e6
Journal	Immunity
Volume	58
Issue number	11
DOIs	https://doi.org/10.1016/j.immuni.2025.09.001
State	Published - Nov 11 2025

Keywords

IL-4
S. aureus
atopic dermatitis
basophil
food allergy
intestinal epithelial cell
intestinal permeability

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10.1016/j.immuni.2025.09.001

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Das, M., Alasharee, M., Woods, B., Mukherjee, S., Kim, S., Elkins, M., Ngo, J., Magin, L., Timilshina, M., Leyva-Castillo, J. M., Murphy, K. M., Anthony, R. M., Laureano, A. F. S., Murphy, G. F., McNamee, S., Brombacher, F., Hogan, S. P., Turner, J. R., Abtahi, S., ... Geha, R. S. (2025). S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis. Immunity, 58(11), 2769-2784.e6. https://doi.org/10.1016/j.immuni.2025.09.001

@article{7980fc283886419f81a2ce0c733f213f,

title = "S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis",

abstract = "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.",

keywords = "IL-4, S. aureus, atopic dermatitis, basophil, food allergy, intestinal epithelial cell, intestinal permeability",

author = "Mrinmoy Das and Mohammed Alasharee and Brian Woods and Saikat Mukherjee and Shira Kim and Megan Elkins and Jacqueline Ngo and Logan Magin and Maheshwor Timilshina and Leyva-Castillo, \{Juan Manuel\} and Murphy, \{Kenneth M.\} and Anthony, \{Robert M.\} and Laureano, \{Ana Fl{\'a}via Santarine\} and Murphy, \{George F.\} and Shannon McNamee and Frank Brombacher and Hogan, \{Simon P.\} and Turner, \{Jerrold R.\} and Shabnam Abtahi and Wanda Phipatanakul and Leung, \{Donald Y.M.\} and Elena Goleva and Oettgen, \{Hans C.\} and Mei Li and Janet Chou and Schlievert, \{Patrick M.\} and Finkelman, \{Fred D.\} and Geha, \{Raif S.\}",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = nov,

day = "11",

doi = "10.1016/j.immuni.2025.09.001",

language = "English",

volume = "58",

pages = "2769--2784.e6",

journal = "Immunity",

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Das, M, Alasharee, M, Woods, B, Mukherjee, S, Kim, S, Elkins, M, Ngo, J, Magin, L, Timilshina, M, Leyva-Castillo, JM, Murphy, KM, Anthony, RM, Laureano, AFS, Murphy, GF, McNamee, S, Brombacher, F, Hogan, SP, Turner, JR, Abtahi, S, Phipatanakul, W, Leung, DYM, Goleva, E, Oettgen, HC, Li, M, Chou, J, Schlievert, PM, Finkelman, FD & Geha, RS 2025, 'S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis', Immunity, vol. 58, no. 11, pp. 2769-2784.e6. https://doi.org/10.1016/j.immuni.2025.09.001

TY - JOUR

T1 - S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis

AU - Das, Mrinmoy

AU - Alasharee, Mohammed

AU - Woods, Brian

AU - Mukherjee, Saikat

AU - Kim, Shira

AU - Elkins, Megan

AU - Ngo, Jacqueline

AU - Magin, Logan

AU - Timilshina, Maheshwor

AU - Leyva-Castillo, Juan Manuel

AU - Murphy, Kenneth M.

AU - Anthony, Robert M.

AU - Laureano, Ana Flávia Santarine

AU - Murphy, George F.

AU - McNamee, Shannon

AU - Brombacher, Frank

AU - Hogan, Simon P.

AU - Turner, Jerrold R.

AU - Abtahi, Shabnam

AU - Phipatanakul, Wanda

AU - Leung, Donald Y.M.

AU - Goleva, Elena

AU - Oettgen, Hans C.

AU - Li, Mei

AU - Chou, Janet

AU - Schlievert, Patrick M.

AU - Finkelman, Fred D.

AU - Geha, Raif S.

PY - 2025/11/11

Y1 - 2025/11/11

N2 - 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.

AB - 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.

KW - IL-4

KW - S. aureus

KW - atopic dermatitis

KW - basophil

KW - food allergy

KW - intestinal epithelial cell

KW - intestinal permeability

UR - https://www.scopus.com/pages/publications/105020804453

U2 - 10.1016/j.immuni.2025.09.001

DO - 10.1016/j.immuni.2025.09.001

M3 - Article

C2 - 41005294

AN - SCOPUS:105020804453

SN - 1074-7613

VL - 58

SP - 2769-2784.e6

JO - Immunity

JF - Immunity

IS - 11

ER -

S. aureus exposure during cutaneous antigen sensitization causes basophil- and interleukin-4-dependent exaggerated food anaphylaxis

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