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February 14, 2017

Ticks’ Tricks for Skipping Tick-Borne Sicks

  • Ticks have attained notoriety for their transmission of Lyme disease, but they have kept secret their ability to survive the dread microbes they carry. Ticks, it turns out, have a distinct immune system, features of which may prove to be subject to manipulation. If the tick immune system were to be strengthened, ticks could become less hospitable to microbes that cause diseases in humans. Also, if the tick immune system were better understood, it might be possible to develop translational approaches that would lessen the harm of ticks visit on people.

    To learn how ticks tolerate a variety of disease-causing microbes—for example, the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale—scientists at the University of Maryland School of Medicine burrowed into details of the tick immune system. These scientists were particularly interested in features that would distinguish the immune system of the tick from the immune systems of insects.

    Scientists had long assumed that the tick immune system works similarly to that of flies and mosquitoes. But ticks, which have existed on the planet for between 120 million and 443 million years, have taken an entirely different path. In evolutionary terms, ticks are as far removed from insects as humans are from fish.

    "Although the two bugs are seemingly alike, it turns out that the immune system of ticks is quite distinct from insects,” explained Joao Pedra, Ph.D., an associate professor of microbiology and immunology at the University of Maryland School of Medicine. “Our [work] clarifies the ins and outs of how the tick immune system fights bacteria.”

    Work accomplished by Dr. Pedra’s group was summarized in an article that appeared February 14 in the journal Nature Communications. The article, “Infection-Derived Lipids Elicit an Immune Deficiency Circuit in Arthropods,” outlines distinct immune pathways the tick uses to activate a protective mechanism called the insect immune deficiency (IMD) network. The IMD network resembles the tumor necrosis factor receptor network in mammals and senses, the scientists indicated, the “diaminopimelic-type peptidoglycans present in Gram-negative bacteria.”

    “Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks,” wrote the authors of the Nature Communications article. “Cell signalling ensues in the absence of transmembrane peptidoglycan recognition proteins and the adaptor molecules Fas-associated protein with a death domain (FADD) and IMD. Conversely, biochemical interactions occur between x-linked inhibitor of apoptosis protein (XIAP), an E3 ubiquitin ligase, and the E2 conjugating enzyme Bendless.”

    After identifying components of the tick immune system, Dana Shaw, Ph.D., the lead author of the current study and a research fellow in Dr. Pedra's laboratory, was able to block the tick immune response with a molecular technique named RNA interference. Dr. Shaw was also able to overactivate the ticks' immune system and thereby enable it to get rid of bacteria even more efficiently.

    The discovery has several exciting implications. By targeting key molecules—essentially manipulating the tick immune system—scientists may now try to make ticks less vulnerable to infection by these microbes. If ticks do not acquire these bacteria in the wild, then they won't be able to transmit the microbes to humans. Dr. Pedra and his colleagues are now pursuing work along these lines to further understand the tick immune response. "This area of research is understudied and we are only beginning to scratch the surface,” noted Dr. Pedra. “That is the beauty of it."

    Of tick-borne diseases, Lyme disease is perhaps the most well known. It exists all over the United States, although it is more concentrated in the Northeast, Midwest, and to a lesser extent, along the Pacific coast. Researchers estimate that between 296,000 and 376,000 people per year are infected in this country. Lyme disease symptoms can include fatigue, muscle pain, joint aches, memory loss, confusion, headaches, and neurological problems.

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