Nav: Home

City mouse-country mouse experiment shows link between environment, worm infections

March 08, 2018

When laboratory mice moved to the countryside where they could burrow in dirt, forage for food and generally live like ordinary mice, they became more susceptible to infection with parasitic whipworms than mice that stayed in the lab, a new study has found.

The longer the mice lived outdoors, the greater the number and size of these intestinal worms -- which are relatives of the human whipworms that infect over 450 million people worldwide, researchers from Princeton University and New York University School of Medicine found. The study was published March 8 in the journal PLOS Biology.

"The study gets at the question of how much we are really learning from highly controlled experiments conducted in artificial environments," said Andrea Graham, associate professor of ecology and evolutionary biology at Princeton, who led the study. Such experiments are often used as precursors to studying diseases in humans.

In the study, outdoor mice also experienced a decrease in the type of immune response needed for expelling the worms, the researchers found. The mice's guts contained a greater diversity of bacteria, including some that may have increased worm-egg hatching and prolonged the duration of infection.

Compared to laboratory mice, mice that moved to the outdoors developed worms that were much longer and fatter. The boost in hatching rates, growth and survival occurred after just 10 days of living outdoors.

Graham and her team have been working on "re-wilding" mice for the past several years by moving them to a semi-rural facility not far from the Princeton campus.

There, mice live in open-air, escape-proof enclosures filled with a variety of native plants that provide favorite foods like seeds, berries and clover. The animals can also get laboratory-style mouse chow anytime they want from a food silo. Wooden huts provide shelter from the rain, and electric fences keep out predators.

In the enclosures, mice face challenges including digging burrows, enduring variable weather, and navigating a complex environment. "Our mice had a lot more to deal with than the typical laboratory mouse," Graham said. "We weren't sure what to expect when we first moved the mice to the farm -- how would they do, after so many generations of lab living?" Graham said. "But within 30 minutes they had found the food silos and were starting to explore."

The facility is one of a few like it in the world, and it is a stark contrast to the sterile and uniform laboratories that researchers use to control experimental variables and keep diseases from spreading in the facilities. The outdoor location allows researchers to explore how the real-world environment affects the animals' immune responses.

In the outdoors, mice developed an immune response that was less capable of combating worms than if the mice had stayed in the lab. Certain lab strains are fairly good at fighting off worms. They develop a "type 2" immune response that involves the gut secreting mucous and moving in such a way as to flush out worms in a "weep and sweep" approach.

The researchers found that this weep-and-sweep response was decreased in the outdoor mice's intestinal cells. The worm burden in the outdoor mice was as heavy as the burden seen in mice of a strain completely lacking the ability to mount a type 2 response. Instead, the outdoor mice had more of a "type 1" response that is more adept at handling viruses and bacteria.

"In the lab, most mice expel the worms within 14 to 21 days," said Jacqueline Leung, a graduate student at Princeton in the Department of Ecology and Evolutionary Biology and the first author on the study. "Three weeks after infection with 200 initial eggs, there were fewer than 10 worms in each of the laboratory mice, which was expected. But the mice in the field were still harboring up to 100 worms and these worms were much bigger in size."

The response may be linked to the types of bacteria that the outdoor mice encounter. These bacteria from the environment colonize the intestines and form a community of microorganisms called the microbiota. The microbiota can spur mice, humans and other hosts to develop immune responses that can help fight infections, previous studies have shown.

The team wondered whether gut microbes acquired from a more natural environment could impact how individuals cope with parasitic worms. The researchers found that compared to lab mice, the country mice's microbiota consisted of a greater range of bacterial species. This greater diversity may have promoted worm growth directly, by providing food for the worms, or indirectly, by harming the country mice's ability to fight off worms.

P'ng Loke, an associate professor of microbiology at New York University School of Medicine, was a co-author on the study. "Mice that have been reintroduced into the wild develop what looks like a different immune system more directed against bacterial infections," Loke said. "The increased activity that we see in the wild may be driven by the microbiota."

The interaction of parasitic intestinal worms and the gut microbiota has gained attention in recent years following reports of individuals who self-dosed with parasitic worms to treat severe colonic inflammation. The strategy involves using worm infection to induce mucous, which coats the colon and protects against inflammation caused by an aberrant immune attack on some members of the microbiota. Leung contributed to the study of one such patient while working with Loke before becoming a graduate student at Princeton.

Future studies at the outdoor facility will continue to explore the relative roles of genes and environment in contributing to inflammatory and infectious diseases.
-end-
The research team included, at Princeton: Sarah Budischak, postdoctoral research associate in ecology and evolutionary biology, Christina Hansen, senior research specialist in ecology and evolutionary biology, and then-undergraduates Mitchell Shellman and Rebecca Neill, both Class of 2016. Also involved in the study were Hao Chung The of the Oxford University Clinical Research Unit in Vietnam and Rowann Bowcutt, then a postdoctoral researcher at the New York University School of Medicine.

Funding for this study was provided by the National Institutes of Health, the National Science Foundation, and Sigma Xi.

Princeton University

Related Immune System Articles:

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.
Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.
COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.