Could worms help us treat chronic inflammatory conditions?
By studying how infectious worms interact with our immune system, we may one day be able to treat diseases like rheumatoid arthritis, inflammatory bowel disease, and even allergies.
By Lisa Osborne, Assistant Professor, UBC Department of Microbiology and Immunology
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2020 is the year of a global pandemic and we’re all hyper-focused on hand-washing, mask-wearing, and social distancing. Creepy crawly critters may be the last things we want to think about. But when the critters in question can impact how your immune system responds to viruses and bacteria, it’s worth a look.
Helminths are a broad family of worms (they’re literally named after the Greek word for worm) that can cause intestinal infections in people, cattle, wildlife, and rodents.
Although helminth infections are uncommon in Canada, most of North America and Europe, approximately a quarter of the world’s nearly eight billion people are infected with a soil-transmitted helminth. These infectious worms get into humans through contaminated soil, mostly in tropical and sub-tropical regions across sub-Saharan Africa, East Asia, and South and Central America.
There are three major subclasses of soil-transmitted helminths — hookworms, roundworms, and whipworms. All of these worms have infectious eggs or larvae. Bathing, farming, trekking through, or eating contaminated food or water are common ways people become infected with these worms.
In both humans and animals used in farming, helminth infection is likely to cause a bout of intestinal discomfort including the unpleasant symptoms of diarrhea, nausea and bloating. However, infections can be much more serious — children with a large worm infection can be anemic, have impaired cognitive development, and even stunted growth.
Luckily, anti-helminthic drugs can treat these parasitic infections and clear them from the body. But unlike the immune response to many viruses or bacteria, helminth infections don’t tend to induce long-lasting immunity. A person can be infected with the same type of worm over and over again. Over a lifetime, these repeated worm infections seem to eventually lead to immunity, but we don’t understand how this happens or why it takes so long. What we do know is that helminth infections change our immune system, in both good and bad ways.
Our immune response is like an army — it has look-outs to warn us of invaders, foot soldiers to deal with the first wave of attack, and generals that coordinate special forces to deal with the specific type of invaders.
If your immune system drives out the invader, you and your immune system can be seen as the victor, vanquishing the enemy. But an alternative outcome is that the immune system and the infecting bug come to a truce. The host essentially cedes some property to the invading pathogen and allows it to co-exist in the body. Why? Well, in some cases, the amount of immune firepower that would be necessary to clear out the invader is incredibly high and could result in significant collateral damage to our own body. Given the choice, it’s more prudent to host a long-term guest, even an uninvited one, than it is to burn your own house down.
Helminth infections fall in the latter camp. They set up shop in our intestines where they have access to nutrients and a protected site to produce new infectious worm babies. Meanwhile our immune system lowers its inflammatory response, a response that would cause tissue damage as it tries to clear the worms from your body.
In some situations, the truce can be dangerous. If your immune system is keyed to down-play your inflammatory responses, any new infection, even a minor cold, might take longer to beat.
In mice, we can reproduce this effect in a lab. Mice with ongoing helminth infections take a longer time to clear out viruses and bacteria. In some cases, the mice get much sicker as a result of this tuned down immune response. In people, these relationships are a bit trickier to study and explain, since we don’t have the same detailed information on when someone was infected with the helminth, bacteria or virus. Understanding the effects of co-infection between helminths and things like HIV and tuberculosis is an active area of research with important health implications for millions around the world.
The upside of helminth’s effects on your immune system (called helminth induced immunoregulation) is that it can limit the development of some chronic inflammatory conditions, at least in mice.
Carefully designed experiments in animals on multiple sclerosis, inflammatory bowel disease, rheumatoid arthritis, and even allergies have shown that a pre-existing helminth infection can delay when these diseases start or even how serious they become. In some ways, this is great news and may help explain why chronic inflammatory diseases, like arthritis and allergies, are more common in far northern and southern countries, where helminths are less common.
You may have heard of the hygiene hypothesis. It suggests that getting dirty and being exposed to a diverse array of microbes, especially those like helminths that have co-evolved with us, can help tune the immune system so that it is less likely to develop autoimmune or other inflammatory disorders.
However, whether the order of operations can successfully be reversed remains unknown. It’s unclear whether someone who already has an autoimmune or inflammatory disease (like multiple sclerosis or allergies) can benefit from introducing worms as a disease treatment.
Unfortunately, despite initial positive results, clinical trials have reported minimal effects of infecting people with helminths on purpose to treat multiple sclerosis, inflammatory bowel disease, allergies, or other inflammatory diseases. It might be a little like building a stable — it’s best to lock the gate first, rather than installing a strong lock once the horse is already out of the barn.
Ongoing research in my lab is attempting to address some of the outstanding questions in this field. For example, we are deliberately infecting mice with helminths to modulate a multiple sclerosis-like disease. Previous studies have identified helminth-induced changes to the immune system that provide some protection from disease, but we are interested in assessing effects of the helminth directly on cells in the central nervous system. At the same time, we are studying how helminth infection can change the intestinal ecosystem. To do this, we use ‘germ-free’ mice that allow us to carefully introduce different bacterial and viral species that normally reside in the gut and assess how their presence and function is changed in response to helminth infection.
Together, these studies could provide new and important insights into how helminths might protect against a specific autoimmune disease. These kinds of insights are needed in order to develop better treatments to help people living with disease once the horse has left the barn.
For more information on helminth infections, their biology, history and potential clinical applications, this podcast has a wealth of additional information.