Staph Aureus on the Skin Associated With Severe Food Allergic Reactions Via a Cascade: IL-33, IL-3, IL-4

People with atopic dermatitis (eczema) often have Staphylococcus aureus (Staph) colonizing their skin, and this has been linked to food allergies. But until recently, the exact way this connection works has been unclear.

A new study published in Immunity (Das et al., 2025) uncovers a surprising chain of events that explains how skin Staph can drive oral anaphylaxis - severe allergic reactions after eating foods.

Researchers observed higher levels of IL-4 (a key allergy-promoting molecule) in the blood of patients with both atopic dermatitis and food allergies. Using mouse models, they showed that when a food protein (like ovalbumin) is applied to the skin together with Staph or its toxin Staphylococcal enterotoxin B (SEB), it sets off a cascade:

Skin cells (keratinocytes) release IL-33.

This prompts T cells to release IL-3.

IL-3 draws basophils (a type of immune cell) into the lymph nodes that drain the skin.

Basophils then produce IL-4, which supercharges dendritic cells to strongly promote Th2 responses (the allergy-driving arm of the immune system).

This leads to elevated systemic IL-4.

High IL-4 weakens the intestinal barrier, making the gut more permeable.

More food antigens leak through, triggering mast cells in the gut and causing exaggerated allergic reactions - including anaphylaxis - to foods the person was sensitized to through the skin.

In short, Staph on inflamed skin doesn't just stay local - it amplifies a Th2 response that "primes" the gut for dangerous overreactions to ingested allergens.

This breakthrough highlights a novel pathway linking skin bacteria to food anaphylaxis and could open new avenues for treating or preventing severe food allergies in people with eczema - perhaps through targeting Staph, IL-4, or basophils.

For the full study: https://doi.org/10.1016/j.immuni.2025.09.001