The Parasitic Worms that Transformed Our Immune System

Newswise — Summer is near, flowers are blooming, and more than one in four Americans have seasonal allergies. But what most people don’t know is that the part of the immune system that causes allergies has been shaped from day one by the most successful human pathogens on the planet: a group of parasitic worms called helminths.

Keke Fairfax, PhD, believes that the best way to understand the human immune system is to understand how it’s evolved to deal with pathogens, especially helminths. “There has never been mammalian immunity without helminths,” explains Fairfax, an associate professor in the Department of Pathology at the Spencer Fox Eccles School of Medicine at the University of Utah. The Type 2 immune system, which is involved in allergic reactions and wound healing, evolved in response to parasitic worms, Fairfax says. “By studying the interaction between the immune system and these pathogens, you can actually understand how the mammalian immune system evolved to function.”

The risks--and benefits--of infection

While helminth infections are relatively rare in the U.S., they’re extremely common worldwide, currently affecting more than 1.5 billion people. They cause chronic diseases such as schistosomiasis, which can lead to malnutrition, liver failure, and death. These diseases present an enormous public health burden globally.

But their relative absence in the U.S. may be causing unexpected negative health consequences. “It’s very clear that helminths drive the development of very specific cells in the immune system, and without that, the immune system does not necessarily develop properly,” Fairfax says.

Parasitic worms produce many chemicals that reduce the activity of the immune system, which helps the worms maintain a chronic infection in their host. For millions of years, our immune systems have evolved to work in the presence of these immune-suppressing chemicals; without them, people may be at increased risk of autoimmune and inflammatory diseases, including asthma and diabetes, Fairfax says. She adds that many immunologists believe that the lower rate of helminth exposure in the U.S. may contribute to the increasing prevalence of these conditions.

But parasitic worms’ immune-suppressing effects can cause problems, too. Worm infection can make some vaccines less effective. And these changes can last long-term—in some cases, even across generations. If someone is infected while pregnant, it can tamp down their kids’ immune responses to measles vaccination. 

Revealing long-term health changes

Fairfax’s lab is trying to unravel the complex relationship between helminth infection and the immune system, uncovering long-lasting health changes that depend on what stage of life the infection occurs in. “There are specific windows in the development of an individual where different cell types are open for reprogramming,” Fairfax explains.

Her lab’s research has identified how, in mice, schistosomiasis infection during pregnancy alters some of the immune signals in the next generation, changing the number of some immune cells and weakening the response to vaccination. She’s also uncovered sex-specific differences in how helminth infection affects metabolism, helping explain why worm infection can protect against metabolic diseases.

Transforming human health

Because helminth infection is less common in the global North, Fairfax adds, it tends to be understudied relative to its importance. But the relatively small community of scientists investigating helminths have made an outsized impact on human health. Research on the interactions between the immune system and helminths was foundational to the development of drugs that affect Type 2 immunity, including the asthma drugs dupilumab/Dupixent and omazilumab/Xolair.

Fairfax says that these translational discoveries underscore the importance of basic science to lead to discoveries that transform human health. “One of the tenets of basic science is that you actually never know, 20 years from now, what a specific finding is going to lead to,” she says. “It’s really hard to predict.”

What’s certain is that, like the helminths she studies, Fairfax has found her niche. She knew she wanted to pursue science at age 6 and started researching pathogens in high school. “Then, in grad school, I found worms,” Fairfax says. “And I haven’t looked back.”