By Margaret Evans

Shetland ponies have an immune response to insect bites that is helping scientists understand how people might be prevented from developing allergies.

Insect bite hypersensitivity (IBH) is a common, seasonal skin reaction that affects a lot of horses of different breeds. At the University of Edinburgh, researchers investigated the reaction to midge bites on Shetland ponies. They found that among some of the ponies, their immune system was able to respond in a way that prevented an allergic reaction. 

It was previously believed that the reason some ponies do not suffer an allergic reaction to bites was because their immune system did not recognize the allergens carried by insects. However, the researchers have demonstrated for the first time that all horses respond but that their immune system can react in two different ways. One response will yield the irritating itching and inflammation which another response will block it. 

Midges are dark insects just a few millimetres long and are often seen rising in clouds in the evening. Both males and females feed on nectar but the female needs a blood meal so that her fertilized eggs can mature. They swarm around water, marshes, wet soil, rotting vegetation or manure, and often bite at dusk or dawn and lay their eggs en masse. The bite is like a sharp prick and a constant irritant to sensitive horses.

Sixteen Shetland ponies took part in the study during the IBH off-season and 19 during the allergy season, basically a winter/summer scenario. IBH affected ponies ranging in age from two to ten years had each been diagnosed by a veterinarian to confirm a clinical history of recurrent skin irritation at the mane and tail with remission during the off-season. The control ponies ranged in age from four to fifteen years and were randomly selected from the same stable with a diagnosis of no sensitivity to midge bites. None of the ponies received any immunosuppressive drugs before or during the testing. 

Photo: ©CanStockPhoto/Base1101658

To collect the midge serum, 300 live female midges were collected then frozen at minus 80 degrees C. The insects were then crushed in a protease inhibitor mixture that protects the integrity of the proteins during extraction. The protein samples were centrifuged for ten minutes then snap-frozen in liquid nitrogen until use.

Prior to injection, blood was collected from each pony to determine its midge-specific antibodies. Each pony was injected with the midge whole body extract. Skin biopsies were taken five minutes, twenty minutes, and twenty-four hours after the allergen injection using local anesthesia. 

The team found that after being exposed to bites, the horse immune system releases various types of cytokines which affect the behaviour of other cells. Cytokines are a broad category of small proteins important in cell signaling. The ponies that reacted to the midge testing (and therefore live midge bites) released cytokines known as lL-4 which trigger allergy symptoms. In ponies not sensitive to bites, another cytokine INFy was released, which blocked different immune cells that would trigger allergic reactions.

Allergies are the result of a complex interaction between genetic and environmental factors. But it’s not fully understood why some individuals develop sensitivities to certain substances and others don’t, or what triggers the immune system to activate a protective response over an allergic one, the team said. 

“To our knowledge, this is the very first study of a natural allergic disease in which we can show that immune responses to allergens can take two directions, either leading to allergy or to tolerance,” said research leader Dr. Dietmar Zaiss with the School of Biological Sciences. “We believe this finding could have direct practical implications, for example by helping immune responses to choose the ‘right’ direction in individuals whom we would like to protect from developing occupation-associated allergies."

What is interesting is that the ponies’ immune response to midge bites is similar to what happens in people with allergies. Understanding what triggers those allergic reactions could help researchers come up with approaches to suppress people’s sensitivities by priming the human immune system to suppress an allergy reaction.

“Our data suggest a novel way of how to prevent the development of allergic diseases, for instance, in individuals in danger of developing occupational allergic diseases,” the team wrote in their report. “Such persons could, for instance, be immunized prior to exposure to the allergen in a way that skews the allergen-specific immune response toward a type-1 immune response.”

The study which was published in the journal PLOS ONE was funded by the Dutch Foundation for Technical Sciences (STW) and was carried out in collaboration with researchers in the Netherlands.

Main Photo: ©Canstockphoto/Zuzule