A scientist won $1.8 million to study how parasitic worms suppress our immune systems with venom to live inside us undetected

adler dillman nematodes
A Steinernema carpocapsae nematode — what the worms look like as they spit venom into a host.
  • Nearly a quarter of the world's population is infected with parasitic worms called nematodes.
  • Some of these parasites can cause blindness or death.
  • But our bodies' immune systems often have no idea they been invaded because the nematodes release a venom that cloaks their presence.
  • The NIH recently awarded parasitologist Adler Dillman $1.8 million to figure out how these worms go undetected in our bodies.
  • Dillman hopes the research could one day help treat autoimmune disorders.
  • Visit Business Insider's homepage for more stories.

 

Adler Dillman is obsessed with worms. 

"I'm a big sci-fi fan, especially the 'Alien' franchise movies," Dillman, a parasitologist at the University of California, Riverside, told Business Insider. "This idea of having something that can be inside you without you knowing seems like something out of those movies, but it turns out we have that kind of stuff on planet Earth."

Indeed, billions of people — nearly a quarter of the world's population — are infected with some kind of parasitic worms, also known as nematodes. These worms for the most part wriggle their way into our bodies undetected. Some can cause blindness, cognitive impairment, and even death.

"You can have a person riddled with infection who never realized there's a 2-centimeter-long worm in their eye and thousands of parasites in their blood," Dillman said in a recent press release about his research. "The immune system never signaled something was wrong. How is that possible? We know very little about how that works." 

In July, the National Institutes of Health awarded Dillman $1.8 million to investigate exactly that — how our bodies get caught with their immunological pants down when it comes to parasitic worms.

So far, Dillman said, what we know is that nematodes exude a venomous spit that helps them avoid detection. By studying how exactly that venom suppresses parts of our immune system, Dillman hopes to help scientists figure out how to better treat deadly autoimmune disorders — conditions like inflammatory bowel disease or Celiac disease.

Dillman is infecting fruit flies with nematodes 

adler dillman nematodes
A nematode releasing venom, which is stained here in blue.

Dillman's research focuses on identifying the specific proteins in a nematode's venom that help it trick a host into ignoring its presence.

"They are masters of modulating the immune system," he said. "My goal is to identify the chemical pathways that allow it to happen."

His lab is looking at 500 or so different types of proteins released by nematodes that infect fruit flies, since "flies are cheaper and easier to work with, and the parasites that affect insects release the same proteins as those that infect mammals," he said. 

adler dillman nematodes
Fruit flies ready to be infected by nematodes.

The research requires infecting the flies with various types of worm venom. That causes some flies to die within hours, since the nematodes that infect insects — unlike those that infect humans — kill their host. But others see their immune response get significantly shut down; that's the process Dillman hopes to figure out. 

But collecting enough venom to do these experiments at all is challenging, he said, since it requires "milking" the microscopic nematodes.

"You need millions to get an appreciable amount of venom," Dillman added. 

adler dillman nematodes
Nematodes infect wax worms.

Worm venom could be used to treat autoimmune disorders

Understanding how nematode venom proteins tamp down a host's immuno-defenses could help researchers develop therapies to treat autoimmune disorders — conditions in which the immune system mistakenly attacks the body.

"There's compelling evidence that having a nematode infection may help regulate a disorderly immune response," Dillman said, adding that past clinical trials have used nematodes to treat Celiac disease, Crohn's disease, multiple sclerosis, inflammatory bowel disease (IBD), and rheumatoid arthritis. 

An analysis of research on this subject, published in 2017, described how the presence of nematodes and other parasites can lower inflammation in IBD and reduce the severity of multiple sclerosis, type 1 diabetes, asthma, and rheumatoid arthritis in animals.

A 2010 study, in fact, described a patient with IBD who deliberately infected himself with a parasitic worm called a whipworm. The man's immune system started producing a type of protein crucial to healing his digestive tract, and the disease went into remission.

Based on that result, the study authors wrote that worm "colonization may have the potential to regulate intestinal inflammation in inflammatory bowel diseases." 

adler dillman nematodes
Juvenile nematodes preparing to infect a larval insect.

It's not hard to imagine why a nematode would want to to control a human host's intestinal inflammation: Many kinds of worms — including hookworm and threadworm — live in our intestines, so an immune response could easily kill the worm or expel it from our body. To avoid this, the nematodes seem to be able to bring the distress under control on their own.

Scientists don't know how they do that, though it's presumably by secreting a cocktail of proteins into their host.

Dillman said such a cocktail "could be explored as an avenue of treatment," given that infecting someone directly with nematodes isn't an appealing idea. 

"But we could one day use these proteins to develop drugs that achieve a similar effect," he added.

adler dillman nematodes
Juvenile nematodes emerging from an infected insect.

A secondary application of Dillman's findings could come in handy for farmers, since some types of nematodes infect and kill insects like beetles and weevils. Some farmers already use the parasites to protect soy crops and cranberries, but Dillman is working on developing a pesticide that uses just their venom.

He's also looking into genetically modifying crops to enable them to secrete a similar toxin on their own to protect themselves from insects.

adler dillman nematodes
What a nematode looks like as it spits venom into a host.

Parasitic worms can 'cause significant reductions in quality of life'

Because parasitic worms don't kill as many people worldwide as other tropical diseases, these infections are largely understudied, Dillman said.

"Nematode infections are, by and large, non-lethal," he added. "Thousands do die from them every year, but millions die from diseases like malaria."

Still, Dillman noted, the parasites can still "cause significant reductions in quality of life."

The hookworm, for example, can cause blood loss and anemia — and "your body really doesn't do anything about it," he said.

An estimated 576 to 740 million people are infected with hookworm, according to the CDC. Hookworms enter through the skin and travel via the lungs to your small intestine, where they live for up to five years as they sexually mature.

Hookworms
Ancylostoma caninum, a type of hookworm, attached to a human intestine.

"When you run around barefoot in the grass near anywhere people have gone to the bathroom outside, they can enter you at that point," Dillman said.

Hookworms thrive in the southeastern US.

Another nematode that commonly infects people is the roundworm, whose larvae you can ingest if you eat undercooked pork or bear meat. One type of large roundworm can grow to the size of a green bean in your digestive tract.

'Nematodes crawling around in the white of her eyeball'

Between 28,000 and 29,000 species of nematodes known to science. Most nematodes are microscopic, though some can get enormous.

"The parasites that infect larger mammals, like whales, can be a meter long and thick as a pencil," Dillman said.

adler dillman nematodes
A mass of juvenile nematodes.

But only 15% are parasites of animals, Dillman said. The rest live in the ground, oceans, and fresh water, fulfilling critical ecosystem functions like recycling nutrients in the soil.

Dillman said his favorite parasitic worm story involves a 21-year-old woman in the UK who felt healthy but went to the doctor complaining about something moving in her eye.

"They find 2-centimeter-long nematodes crawling around in the white of her eyeball," Dillman said, adding, "blood tests showed she had thousands of larval nematodes throughout her body."

Doctors identified the nematode as loa loa, also known as the African eye worm. It's not found in the UK — it turned out the patient had taken a trip to Nigeria six years earlier, and the worms had lived in her body undetected since then, with her immune system none the wiser.

adler dillman nematodes
Adler Dillman, a parasitologist at the University of California, Riverside.

After eye surgery and treatment with corticosteroids, the patient was declared nematode-free.

"The human immune seems unbeatable, and yet these parasitic worms can infect you and completely hide," Dillman said. "That's freaking wild."

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