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When a tick starts to feed, it doesn’t suck blood out of blood vessels. Instead, it secretes enzymes in its saliva that destroy a small ring of host tissue. This creates a “feeding cavity,” which Ribeiro likens to a “lake of blood.” “The tick sucks blood from that lake,” he says. For this strategy to work though, ticks also need to make proteins that prevent blood from clotting, as it normally wants to do in an injury site. Over the course of days, a host’s body will try to heal the wound by sending cells that make collagen. Normally, this would allow the wound to scar over, but tick saliva has molecules to counteract this, too.
Lastly, the tick has to evade a host’s immune system. Mammals, including humans, have complex immune systems with multiple lines of defense, and tick saliva can neutralize pretty much all of them. To start, ticks secrete molecular “mops,” which bind to and neutralize histamine. Histamine is best known for causing itching and redness, but it also plays an important role in opening up blood vessels to allow immune cells to get to a site of injury. Tick saliva prevents this, so tick bites don’t itch and immune cells can’t get to the bite. Tick saliva also degrades pain-inducing molecular signals in a host. That’s why tick bites also do not hurt. Ticks then inject molecules that neutralize or evade a suite of white blood cells that would otherwise be eating or attacking an invader.
The exact cocktail of a tick’s saliva proteins changes every few hours, Ribeiro says. The thousands of proteins in its saliva are highly redundant in function, and the tick cycles through them as a way of circumventing a host’s immune system. Immune systems take time to recognize and react to a foreign tick protein, and this strategy simply doesn’t give a host’s cells a chance to do that. Suppose, Ribeiro says, “Monday a tick starts feeding on you and injecting the saliva in you.” By Friday, when your body can mount a proper immune response against those first proteins, “the tick has already changed the repertoire.”
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Ticks, of course, are noteworthy not just because they bite, but because they transmit diseases when they bite—including Lyme disease, babesiosis, Rocky Mountain spotted fever, and many, many others. And pathogens may take advantage of the fact that tick saliva suppresses a host’s immune system. Bonnet has found that ticks carrying the bacteria for cat-scratch disease (which, despite the name, is also transmitted by ticks) make more of a saliva protein called IrSPI. In a recent preprint, which has not yet been peer-reviewed, her team isolated IrSPI and found that it suppresses multiple types of white blood cells, weakening a host’s defenses at the bite. The upshot is that ticks can feed undetected, and bacteria can spread into a new host undetected. Tick saliva seems to help not just ticks, but the bacteria that live inside them.