Parents and researchers have long puzzled over the question of why children who grow up in the countryside suffer from fewer allergies, and less frequently from asthma. The previous assumption was that, in some way, the immune system needs the dirt and dust in the country to train itself up. As described in the Journal of Allergy and Clinical Immunology (12 July 2010, online), the researchers from the Ruhr University Bochum together with colleagues from Munich and Borstel have now given this assumption an empirical basis. It appears that a substance found, among other places, in house dust, can prevent the immune system from overreacting, at the very least when it is inhaled in high concentrations in the first year of life. The researchers will now investigate whether the so-called arabinogalactans could be used to prevent or treat allergies and asthma.

During an allergy, the immune system reacts abnormally strongly to the presence of foreign matter, known as allergens. Be it house dust, pollen, animal hair, or food, there’s a whole range of substances that can trigger an allergic reaction. The variety of substances that can cause allergies is a broad as the subsequent symptoms. These can range from allergic rhinitis, itching and burning in the eyes, allergic asthma, skin reactions, and gastrointestinal complaints. Depending on the type of allergy, the reaction can occur immediately, a few minutes or hours, or even days later.

A molecule from the dust
The number of allergies is increasing worldwide. Asthma is the most common chronic disease in children, affecting about five percent of adults and up to ten percent of children. Scientists have long pondered how to explain this increase. Some researchers believe that some of todays Hospital in Munich, have now provided a sound basis for the speculation surrounding this question. The biotechnology company Protectimmun AG, founded in Bochum in 2007, also participated in the study.

In dust samples taken from animal stables, the researchers identified a molecule that could be responsible for protecting children living in the country against allergies and allergic asthma. If it is inhaled in high concentrations during the first year of life, the substance appears to prevent the immune system from excessive immune reactions. At least, this is true in mice.

Needle in a haystack
“The search for the protective substance was like finding a needle in a haystack,” says study head Marcus Peters. For his work, he turned to an unusual source of dust that had been collected in the stables of farms in Germany, Austria and Switzerland. An analysis of the dust showed that it was largely composed of vegetable matter, including more than ten percent arabinogalactan, a plant sugar molecule that is not only extremely common, but also very large. The scientists quickly suspected that the molecule was interacting in some way with the immune system. The molecule is found in large quantities in forage crops such as Alopecurus pratensis, otherwise known as Meadow Foxtail.

Preventing a zealous response by the immune system
The researchers examined how the immune system of mice reacted to potential allergens when arabinogalactan molecules were present. “It was demonstrated that the dendritic cells change their behaviour in the presence of arabinogalactan,” says Peters. Dendritic cells are part of the body’s immune response, and are responsible for presenting harmful invaders to other immune cells, so that they know what to attack. The arabinogalactan appears to make sure that these leaders of the pack suddenly act in a more restrained manner, says Peters. “They produce a specific messenger substance that dampens the immune response.”

The precise receptors on the dendritic cells that are responsible for this mechanism remain to be investigated. Sugar receptors are generally important for the detection of foreign particles by the immune system. “The weakening of the immune response in such a manner is not new to us,” explains Peters. “Even some bacteria take advantage of the mechanism to moderate the immune response of the host.” Arabinogalactans only serve to prevent an over-response by the immune system – the weapons employed by pathogens continue to function as usual.

The dose is what matters
The fact that a substance that derives from grass protects against hay fever has not surprised the researchers: “It's a matter concentration,” says Peters. “In smaller concentrations, grass pollen from Meadow Foxtail can cause allergies: in large doses early in life, however, these reaction’s can also be prevented. Nothing more than increased dosage is indeed the strategy for hyposensibilisation.” The researchers will now investigate whether arabinogalactan can be used for prevention, or for the treatment of allergies and allergic asthma. If the substance is proven in humans, it could open up a whole new means of combating allergies. Even patients would not have to become accustomed to the substance: Because it is soluble in water, convenient applications as sprays or nasal drops are entirely feasible.

In the meantime, the researchers are continuing to search for new active ingredients for controlling allergies in the stable dust. For example, the Munich-based researcher Erika von Mutius and her team, which was also involved in the current study, have already isolated a variety of species of stable-derived bacteria that, following contact, provide protection against allergies in mice.

• Sugar molecule protects country children from allergies