Immune cells rush to gut in food allergy

In battling disease, white blood cells called eosinophils play a supporting role to their better-known immune system partners, T cells and antibodies. Scientists know that eosinophils work diligently against some parasites. Beyond that, their role remains mysterious. This much is clear, however: Eosinophils can make trouble for their host.

Researchers report in the April Nature Immunology that allergic reactions to food coincide with an accumulation of eosinophils in the small intestine. In a study of mice, the scientists found that such a buildup contributes to intestinal inflammation, damage to nearby nerves, weight loss, and a stoppage of digestion.

The mechanism underlying food allergies is not fully understood. The new findings provide evidence linking eosinophils to “real damage to the gut structure of mice,” says study coauthor Eric B. Brandt, an immunologist at Children’s Hospital Medical Center in Cincinnati. In people with food allergies, an influx of eosinophils may partly explain the chronic distress they feel after eating, he says.

Brandt and his colleagues induced an allergy to chicken eggs in a group of mice by injecting them with ovalbumin, an egg protein. Then they fed the mice ovalbumin, placed within coated pill-like beads to prevent the protein’s destruction in the stomach. The mice became unable to digest food, a sign that they were suffering a severe allergic reaction. A control group of mice that weren’t allergic to ovalbumin showed no signs of distress when fed the beads.

Concentrations of eosinophils in the small intestines of the allergic mice were more than double that in the control mice. Some eosinophils drawn to the site released granules that contain toxins, Brandt says. Normally, these would be aimed at parasites or other true adversaries. In this case, the toxins and possibly other immune agents mobilized by the reaction caused inflammation of the intestine.

To move food through the gut, a person must have functioning nerves that signal the intestinal muscles to contract. If present in people with allergies, the kind of intestinal-nerve damage seen in the allergic mice may be responsible for people’s pain and digestive problems, Brandt says.

At the heart of the eosinophil stampede is eotaxin, an immune protein that attracts eosinophils. In allergic reactions induced in the mice, cells in and around the small intestine released excess eotaxin in response to ovalbumin. The concentration of eotaxin within the small intestine of the animals was roughly 4 times that in the controls.

To ascertain the importance of eotaxin in inciting eosinophils to invade the intestine, the scientists performed a separate experiment using mice genetically engineered to lack eotaxin. The researchers first induced ovalbumin allergy both in these mice and in a control group that had normal eotaxin concentrations. When all the mice were fed the ovalbumin beads, significantly fewer eosinophils migrated to the small intestine in the mice lacking eotaxin.

Eotaxin is an immune-signaling molecule called a chemokine. While most chemokines have backup versions that take their place if they are missing, eotaxin seems to lack such redundancy, says immunologist Kent T. Hayglass of the University of Manitoba in Winnipeg.

This uniqueness could make eotaxin a good target for new drugs designed to control food allergies, says allergist Donna L. Bratton of the National Jewish Medical Research Center in Denver.