A Small Worm Offers Big Clues About the Human Immune System
Pew fellow’s research lays a foundation for new strategies to protect against viruses
Human immune systems are intricate disease-fighting networks that begin forming in utero—in the womb before birth—to keep us healthy. Research shows that a mother’s environment and exposures during pregnancy can significantly affect how an infant’s immune system develops. Scientists such as Krist Antunes Fernandes, Ph.D., a Pew Latin American fellow, are exploring this process to better understand how to protect babies from disease.
Dr. Antunes Fernandes’ work in Dr. Ai Ing Lim’s lab at Princeton University looks to one unlikely organism for answers: helminths, also known as parasitic worms. Though helminths have largely been eliminated from most urban environments today, these small organisms once offered a helping hand in bolstering human immune systems—and their biology provides a blueprint scientists can use to craft new therapeutics that keep babies healthy.
This interview was edited for length and clarity.
Q: Your work examines “maternal offspring immune crosstalk.” What is this?
A: Our immune system and barrier tissues—such as the lungs, gut, and skin—start to develop in utero. Emerging data from our lab and others tells us that maternal exposures during pregnancy and lactation actually influence this crucial development and, therefore, the offspring’s immunity throughout life. We call this process maternal offspring immune crosstalk.
Q: What kinds of exposures affect immune development?
A: One of the most important is our contact with microbes. Our immune system and barrier tissues are programmed through exposure to a range of microbes and microparasites. However, urban living, sanitation, and deworming treatment have all led to a dramatic decrease in human interaction with microbes, specifically in key developmental windows such as pregnancy. One specific microparasite that has been disappearing from our society are helminths. These are what we study in the lab.
Q: Tell us how you research helminths.
To model the human populations with chronic gut infections caused by helminths, we infect female mice with Heligmosomoides polygyrus, a common parasitic worm found in nature. Then, we analyze immune outcomes in their babies right after birth and also when they become adults by challenging their immune system with viruses, such as respiratory syncytial virus (RSV). We compare these mice to our control group: mice whose mothers weren’t exposed to helminths.
Q: What have you found?
A: We saw that the exposed offspring were protected against both RSV and influenza. Specifically, we found that this helminth infection in the mother transforms the epithelial cells that line the baby’s lungs. These cells protect against viruses by producing a powerful antiviral protein that we didn’t see in our control group.
Q: So the baby mice don’t get sick at all?
A: Exactly. When I infect them as babies, they don’t get sick. When they become adults, the mice do get infected, but they develop a very mild infection compared to the control offspring. Importantly, the worms themselves don’t get passed from the mother to the offspring—just these protective benefits.
Q: What causes this protection?
A: These helminths change the mother’s microbiota—the bacteria living in her gut—and the offspring inherit this unique microbiota signature. Microbiota produce molecules called metabolites. When we analyzed the feces and blood serum of baby mice, we identified the specific metabolite that causes these protective benefits that we didn’t observe in mice with untreated mothers.
Q: Can these findings be applied to human health?
A: Yes. This is the most important part of this work because, of course, we don’t want to reintroduce a worm into our society. Instead, we want to ask: How can we reintroduce this missing information from our evolutionary partners? What’s exciting is that not only did we discover the metabolite that causes these immune benefits, but we also found that it’s safe for use in human treatment.
Q: So this metabolite could be used therapeutically?
A: Yes. In fact, we put out a patent for this metabolite as an antiviral drug for babies. It’s going to be something we can use in the future as a safe, preventive treatment. If an infant is identified as high-risk for developing an upper respiratory viral infection, such as in preterm birth, we might be able to provide treatment using this metabolite so the baby can be protected throughout its life.
Q: This sounds like exciting work. Where do you hope to take this research next?
We’re getting ready to publish these findings soon. I think it's going to be a very nice contribution to the scientific field. Then, I’m excited to return to Brazil to start a faculty position and launch my own lab. I'm a nutritionist by training, so I’m planning to look at how diet influences microbiota and immune function in offspring. I’ll be working with human cohorts, and we can start treating babies with our patented therapy. It’s going to be a very interesting next chapter.
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