HMN 2026: How Parasitic worms may help scientists develop therapies for inflammatory conditions

A parasitic worm might be the impetus behind a new generation of medicine. In a recent review in published in Clinical & Translational Immunology, Neima Briggs, MD, Ph.D., instructor of medicine (infectious diseases) at Yale School of Medicine, found that certain types of parasitic worm infections, called helminths, diminish the body’s ability to respond appropriately to vaccines, cancer and coinfection. At the same time, their immunosuppressive capabilities may also help scientists develop more effective therapies targeting inflammatory conditions, including allergies and autoimmune diseases.

Globally, about 1 in 4 people is infected with a helminth. Helminths, which include tapeworms, flukes and roundworms, vary in length from 1 millimeter to 15 meters (about 0.04 inches to 49 feet). They are primarily transmitted in areas with poor sanitation through fecal-oral contact and infect internal organs such as the intestines, gastrointestinal tract or lungs, depending on the type of worm.

While helminth infections can cause tissue damage, they do so in a way that the host can tolerate and may not manifest as a particular disease. Helminths can survive for years in their host by weakening a person’s immune response, preventing the immune system from developing meaningful protection, according to the review.

“Helminths are the epitome of misunderstood,” Briggs says. “They have a high rate of infections but low mortality of their host. As an immunologist, I’m fascinated by how they’ve found a way to co-evolve with us.”

Helminth infections manipulate the body’s type 2 immune response, which is triggered by damage to protective body tissue and the release of alarmins, pro-inflammatory signals. Because helminths need to remain in the host to survive, they have found a way to dial down this inflammatory, parasite-fighting response and shift the host into a more regulatory state. This helps the host, too—when people are repeatedly re-exposed to worms, it is less harmful to tolerate an isolated infection than to constantly fight it. Briggs calls this trained tolerance.

“Helminths are masters of regulating the host immune response,” Briggs says. “It’s not a fluke; most species of helminths have found distinct ways to accomplish this.”

What makes helminths such successful parasites gives researchers clues about unexplored pathways and mechanisms in the immune system. The Briggs Lab is focused on pinpointing how the helminth induces trained tolerance in a host and on exploring new ways to treat inflammatory conditions.

Currently, Briggs is working on improving vaccine efficacy for people with a current or previous helminth infection, who have been shown to have a weakened response to vaccines. This effect is most notable with live vaccines such as the measles vaccine and the BCG vaccine for tuberculosis, where both the magnitude and durability of vaccine responses are blunted, according to Briggs.

Helminths are sparking research questions in many aspects of human health, including cancer, for instance—three helminths are classified as human carcinogens, Briggs says. His review suggests they may influence cancer development because they persistently injure tissues and interfere with the repair response. They may also be modifying immunity that protects against the development of tumors. More research is needed to define the role helminths play in cancer risk and progression.

In autoimmune diseases such as Crohn’s disease and type 1 diabetes, research shows helminths may have protective effects by suppressing certain types of inflammation and disease progression. Efforts are underway to translate this potential into a safe therapeutic.

“These are parasites, but they have an interesting story to tell that can help us advance human health,” Briggs says.

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