The new finding advances the search for effective tick bite prevention.
Image Credit: Edwin Remsberg
University of Maryland-led research identified a specific biological pathway that promotes immunity to tick bites in some animals after repeated exposure. The pathway successfully counteracts ticks’ natural ability to feed, further emphasizing the mechanism that could help researchers develop new preventive measures to defend against tick-borne illnesses.
The research was published October 21, 2026 in the Proceedings of the National Academy of Sciences (PNAS).
“Ticks are remarkably successful blood feeders that can parasitize almost every vertebrate. We are interested to learn how some of the incidental hosts mount protective responses against repeated tick bites, and can these natural defenses be harnessed to prevent vector feeding and reduce the risk of pathogen transmission?” said Chrysoula Kitsou, an associate research professor in the Department of Veterinary Medicine at UMD, and the lead author of the study.
Ticks are host to a wide variety of diseases such as Lyme disease and Alpha-gal syndrome, that have a significant impact on human health globally. While vaccines and preventative measures against these illnesses remain elusive, a strategy that prevents or reduces tick bites in the first place would provide broad protection against the full array of tick-borne diseases.
Previous studies have shown that certain animals such as guinea pigs and humans can build resistance to tick bites through repeated exposure, meaning their skin reacts to prevent the tick from feeding and it falls off before it can transmit disease. However, the biology behind this resistance is not fully understood. So, the researchers went on a hunt for the molecular mechanism at work.
They found that the host protein IL36γ is a primary driver of the inflammatory response which prevents a tick from feeding. Then they demonstrated that interfering with IL36y in guinea pigs reversed the animals’ natural acquired immunity. Finally, the researchers induced immunity in mice (through gene editing and other methods), which don’t naturally acquire it, by silencing the pathway in their skin that naturally blocks IL36y.
“I am particularly excited about our findings that offer a new conceptual framework for understanding the immunological mechanisms underlying acquired tick resistance in mammals,” said Utpal Pal, MPower professor in the Department of Veterinary Medicine at UMD, and the corresponding author of the study. “We integrated immunology, genomics, and genome editing to develop several valuable experimental resources. These efforts and resources will facilitate broader investigations into host-vector-pathogen interactions and may ultimately inform innovative strategies to mitigate the burden of vector-borne diseases.”
