To fight Lyme disease, looking to the source

Researchers study the tick immune system for ways to stop illnesses

Blood-sucking ticks may hold the key to preventing Lyme disease in humans.

That was the thinking behind a three-year study by researchers at the University of Maryland School of Medicine that found the ticks harbor bacteria and viruses without consequence until they pass them on to humans when they bite.

“We thought maybe if we understood how the tick immune system worked, maybe we could devise new strategies to avoid infections in humans,” said Joao Pedra, an associate professor in Maryland’s department of microbiology and immunology.

Pedra led the research, recently published in the journal Nature Communications, that outlined for the first time how black-legged ticks survive while harboring the diseaseinducing bacteria such as the cause of Lyme disease. The researchers learned the pathway the bacteria take in ticks, and they were able to manipulate the tick’s immune system to get rid of the microbes.

The results could serve as building blocks for developing preventive measures that could stop some 300,000 people a year from contracting Lyme, a disease of particular concern in the Northeast and upper Midwest that causes flu-like symptoms and other complications.

Lyme disease has been linked in up to 10 percent of cases to another chronic, sometimes debilitating autoimmune condition that researchers refer to as post-Lyme treatment syndrome, which develops after the initial infection has been treated.

Doctors and researchers say preventing Lyme and other diseases would be preferable to trying to treat the conditions. Pedra has some ideas about how scientific discoveries from his lab may eventually contribute to prevention efforts.

One avenue could be a vaccine that protects people by producing an antibody in humans that is transferred to feasting ticks so they don’t feed well and fall off before they can pass on a germ. Another path could involve spraying areas such as yards, much like people do for mosquitoes. The spray would contain a compound triggering the same over-activity in the ticks’ immune system that the Maryland researchers caused in the lab, preventing them from harboring threatening microbes.

Mark Soloski, a Johns Hopkins professor of medicine and co-director for basic research in Hopkins’ Lyme Disease Research Center, said Pedra’s research was important in explaining the tick immune system, which some were surprised to learn is closer to a spider’s system than that of an insect.

There will be challenges, however, for other researchers in translating the science into specific preventive measures, he said. One challenge he and Pedra both noted was the tick’s relatively long life cycle of two to three years, which makes manipulating and studying ticks more laborious compared with mosquitoes that live less than two months.

The researchers also recognize that when they alter any creature’s systems or genetics — even a tick’s — they need to consider unintended consequences for people and the environment.

Other scientists are looking at a variety of means to prevent the spread of Lyme and other tick-borne diseases, including exploring other types of vaccines against tick-borne infections and even genetically manipulating mice that serve as “reservoirs” for bacteria and viruses. Mice routinely collect bacteria and viruses from infected ticks and pass them on to uninfected ones when they are bitten. Soloski said the efforts are worthwhile. “If you chip away at the front end, fewer people will get sick,” he said. “Some people get really sick and have difficulty in coming back from an infection.”

Doctors aren’t entirely sure why some people suffer chronic effects from Lyme, said Dr. John Aucott, an internist and director of Hopkins’ Lyme Disease Research Center. Some doctors have even rejected the idea that Lyme has lasting effects or is connected to another disorder, though that thinking is changing.

Aucott said it’s possible the Lyme bacteria can hide somewhere in a patient’s body, resisting antibiotics. More likely, delayed treatment causes the bacteria to trigger post-Lyme treatment syndrome.

“There are a lot of cool and interesting ideas,” said Aucott, who runs one of the few centers studying ongoing effects from Lyme. “But we have a ways to go.”

Thomas Mather, director of the University of Rhode Island Center for Vector-Borne Disease and one of the scientists working on a vaccine, said Pedra’s research could prompt more efforts.

For his vaccine, he initially thought about creating something to make people itch when they were first bitten by a tick, an immune reaction that is typical of people who have been bitten previously. The alert allows people to remove a tick before it can transmit germs, usually after a day or so into its multi-day human blood meal.

Mather now said he would like to go further and use a protein from tick saliva to develop a vaccine that elicits an immune response in people that prevents them from being infected with any tick-borne microbe.

He said those efforts are a bit “pie in the sky” for now. In the meantime, Mather helps update a website for the TickEncounter Resource Center that offers simple tips to prevent tick-borne infections.

For example, he said, many people don’t know young ticks are poppy seed-sized and typically crawl over someone’s shoes and up their pants, while adult ticks might be more likely to crawl up an untucked shirt. Spray tick repellent inside clothes and check closely for ticks after being outdoors, he recommended.

The researchers say they are optimistic some preventive measures will eventually be developed.

“I’m sure there are approaches we haven’t even imagined,” said Dana Shaw, a research fellow in Pedra’s laboratory and an author of the study. “We’ll see what develops in the next five to 10 to 20 years.”