Australian researchers have identified a novel class of protein found in the saliva of ticks that can switch off the body’s inflammatory response. They say the discovery could lead to a new generation of anti-inflammatory drugs.
Tick saliva and the variety of evasins – anti-inflammatory proteins – it contains have been the subject of research for years. In 2017, researchers from the University of Oxford found that a particular evasin, P991_AMBCA, reduced the inflammation associated with myocarditis. In 2020, University of Sydney researchers successfully synthesized evasins from scratch. And in 2022, a team from Australia’s Monash University unlocked the structural basis for how evasins produce their anti-inflammatory effects.
Now, Monash University researchers have taken their research a step further, identifying a new class of the salivary protein and repurposing it to produce a wide-ranging anti-inflammatory effect.
Ordinarily, when a creepy-crawly bites into human tissue, the tissue releases chemokines, a large family of signaling proteins that recruit white blood cells to produce an inflammatory response. But ticks are unique. Their saliva contains a cocktail of evasins that inhibit the host’s chemokines, thereby suppressing inflammation at the bite site and allowing the tick to feed off its host unnoticed.
“It turns out that ticks have naturally evolved the ability to block chemokine-driven inflammation, which enables them to live on their hosts for extended periods without the host being aware of them,” said Ram Bhusal, one of the study’s corresponding authors.
There are four families of chemokines, but the two main ones are CC and CXC. And there are two classes of structurally different evasins, class A and class B, which target specific chemokines. Class A evasins target CC chemokines, whereas class B target the CXC variety. Both classes produce anti-inflammatory effects. Class A evasins are further divided into subclasses, A1 and A2, produced by different kinds of ticks.
In the current study, the researchers identified a new class, A3 evasins, produced only by the genus Amblyomma, a species of hard tick. They found that these novel evasins recognized a broader range of CC chemokines than most of the evasins discovered to date.
Engineering the structure of A3 evasins, the researchers were able to inhibit the chemokines involved in the common inflammatory diseases, atherosclerosis and rheumatoid arthritis. Atherosclerosis is the deposit of fatty and other materials on the inner walls of the arteries, which can result in a heart attack or stroke, while rheumatoid arthritis is an auto-immune disease where the body’s immune system attacks its own tissue, including joints.
This proof-of-concept study has laid the foundation for developing engineered evasins that might be used to treat inflammatory conditions, the researchers say. Evasins are all the more important because no other treatment directly targets chemokines.
“The tick-derived evasins represent a novel class of anti-inflammatory agents with a distinct mode of action to inhibit chemokines,” Bhusal said. “As such, they offer a fresh perspective and an alternative strategy for reducing inflammation in the body.”
While the study’s findings are promising, further research, including human trials, is needed.
“This finding is significant because it opens up possibilities for developing a new generation of anti-inflammatory drugs,” said Martin Stone, a corresponding author. “These new drugs could improve the treatment options for patients with chronic inflammatory diseases, potentially saving lives and reducing suffering.”
The study was published in the journal Nature Communications.
Source: Monash University