Rare in the body and hard to study, immune cells called basophils have long gotten short shrift from researchers. But a study now shows that basophils help repel bloodthirsty ticks that can spread lethal diseases. The work also introduces a new method for teasing out further immune functions of the often-overlooked cells.
Many animals develop some resistance to ticks the first time the parasites feast on their blood. During later feedings, fewer ticks latch on to resistant animals, and parasites that do attach sup less blood and sometimes even die. Resistance provides another benefit, reducing the odds that ticks will transmit pathogens to their hosts. Some evidence indicated that basophils play a role in tick resistance, but other research pointed to different cells called mast cells. So identifying the key protector has been difficult.
In the new work, immunologist Hajime Karasuyama of the Tokyo Medical and Dental University Graduate School in Japan and colleagues tracked basophils in mice troubled by ticks. When animal were first attacked by the parasites, the cells rarely homed in on tick bites. But if the animals were on their second infestation, the basophils, which normally circulate in the blood, swarmed to the bites and huddled around the parasites' mouth parts. The team then experimented with two ways to temporarily remove the cells from a mouse's circulation. First, the researchers used an established method, injecting mice with antibodies that glom onto basophils. Tick resistance disappeared in these rodents. These antibodies, however, also eliminate mast cells, which made it impossible to determine which cells were providing the benefit. To target basophils, the researchers devised a new technique: they genetically engineered mice so that their basophils carried a receptor for the toxin produced by the diphtheria bacterium. Giving such a mouse a dose of diphtheria toxin destroys the animal's basophils for 5 to 6 days—and banishes resistance to ticks, the scientists report today in The Journal of Clinical Investigation . "Now, we know that the basophil is quite important to acquired tick resistance," says Karasuyama.
Mast cells are also essential for tick resistance, the researchers showed. The team suggests that basophils are necessary to trigger the response, whereas both kinds of cells help turn away ticks. Whether mast cells and basophils collaborate or operate independently to foil the parasites is still a mystery. The tick work is part of a surge of new research on basophils, some of it suggesting that they orchestrate immune responses to parasitic worms and raise the alarm during bacterial infections. The lack of a method for selectively eliminating basophils, leaving mast cells intact, had slowed studies of their functions. But immunologist Donald MacGlashan of Johns Hopkins University School of Medicine in Baltimore, Maryland, says the genetically modified mice created by Karasuyama's team are a "fabulous tool" to probe what else these elusive cells do in the body.