Researchers uncover novel immune mechanism that protects the intestine
By studying intestinal worms, scientists from The Institute make a breakthrough in gut immunity—opening the door to improved treatments for global digestive disorders.
A team of scientists at the Research Institute of the McGill University Health Centre (The Institute) has made a landmark discovery that sheds light on how the immune system protects the gut during infection. By studying intestinal worms—also known as helminths—the team, led by Professor Irah King, uncovered a previously unknown immune mechanism that preserves intestinal function in the presence of persistent infection.
Their groundbreaking finding, recently published in the journal Cell, could pave the way for new treatments for helminth infections, which affect over two billion people worldwide at some point in their lives, as well as for other intestinal diseases. The results could also help revisit older therapeutic strategies that were previously dismissed due to an incomplete understanding of biological processes.
“One way our immune system protects us is by destroying viruses or bacteria. However, some pathogens, such as helminths, have found ways to avoid being killed by our immune system. They can remain in the intestine for months or years without causing disease,” explains Prof. King, PhD, Senior Scientist in the Translational Research in Respiratory Diseases Program at The Institute.
“Puzzled by this paradox, we investigated how the immune system tolerates helminth infection, in the hope of revealing the cellular pathways that mediate this form of host defence. Our finding has broad implications, as it could potentially help fight various pathogens and diseases that cause intestinal damage.”
The fundamental role of interferons in protecting organ function during infection
In this study, Dr. King’s team examined helminth infections in mice and discovered that interferons—immune signals best known for their role in defending against bacterial or viral infections—were produced during helminth infection.
Surprisingly, however, the researchers found that they had no impact on the worms themselves. Instead, interferons signalled to the stroma—a group of cells that form the shape and structure of our organs—to control the damage caused by the worm and ensure that the intestine could continue to function.
To confirm these observations, the team used genetic approaches to block stromal cells from receiving interferon signals. Under these conditions, helminth infection caused intestinal bleeding and severe impairment of the digestive system, demonstrating the critical role of interferon signals in protecting the intestine.
The intestine, a target of constant threats
The intestine is continuously exposed to damage from infections, surgical complications and chronic inflammation triggered by poor diet, pollutants and other environmental stressors. According to the 2019 Global Burden of Disease Study, which analyzed data from 204 countries and territories, digestive disorders affect approximately 35 percent of the global population. Among these, intestinal (or enteric) infections remain the leading cause of death from digestive diseases worldwide.
“This staggering statistic reflects the impact of widespread antibiotic use, diets high in processed foods and rising infection rates linked to overpopulation—human activities for which our intestines are paying the price,” says Prof. King, also Professor in the Department of Microbiology and Immunology at McGill University, and Director of the McGill Centre for Microbiome Research.
Excessive intestinal damage can lead to scarring, called fibrosis, which diminishes intestinal function and affects digestion and nutrient absorption. Over time, the buildup of scar tissue and poor digestion can result in chronic inflammatory bowel diseases, such as Crohn’s disease.
“The scientific and medical communities are struggling to find ways to treat intestinal damage without resorting to major surgery or aggressive medications,” says Susan Westfall, a postdoctoral fellow in Dr. King’s lab at The Institute and the study’s lead author. “What makes our research unique is that it looks at how the immune system functions within the architecture of the intestine itself. Our findings will be particularly relevant in developing nations, where intestinal infections are widespread, and could also inform treatments for other prevalent intestinal diseases, like inflammatory bowel disease, here in Canada.”
A discovery fueled by curiosity, insight and teamwork
While studying parasitic worm infection in mice, the researchers began noticing unexpected macroscopic physical changes in the intestinal tissue—differences they couldn’t immediately explain. These observations prompted deeper investigation into how the immune system might be communicating with stromal cells to preserve organ function in the face of infection. Discussions and collaborations with colleagues at The Institute, including stem cell biologist Alex Gregorieff, immunologist Maziar Divangahi, and infectious disease specialist and researcher Donald Vinh, as well as a host of international scientists with diverse expertise, ultimately led to the discovery of this novel immune mechanism.
The authors note that most research focuses on ways to prevent or eliminate infectious diseases. Few address the collateral damage that occurs during infection and can compromise organ function, resulting in long-term disability or resistance to conventional therapies. Their finding opens a new perspective in our understanding of host defence.
“Over the next few years, it will be interesting to explore whether the protective immune pathways we’ve uncovered can be exploited in vaccines that promote tolerance to infection or in therapies for inflammatory diseases such as cancer, inflammatory bowel disease and fibrosis, where uncontrolled stromal cell activation leads to organ dysfunction,” says Prof. King.
About the study
The study A type 1 immune-stromal cell network mediates disease tolerance against intestinal infection was conducted by Susan Westfall, Maria E. Gentile, Tayla M. Olsen, Danielle Karo-Atar, Andrei Bogza, Franziska Röstel, Ryan D. Pardy, Giordano Mandato, Ghislaine Fontes, De’Broski Herbert, Heather J. Melichar, Valerie Abadie, Martin J. Richer, Donald C. Vinh, Joshua F.E. Koenig, Oliver J. Harrison, Maziar Divangahi, Sebastian Weis, Alex Gregorieff and Irah L. King.
This research was funded by the Canadian Institutes of Health Research (CIHR), which also provided fellowship support for Susan Westfall. Additional support for The Institute’s Gnotobiotic Animal Research Platform—an essential resource for carrying out the study—was provided by the McGill Interdisciplinary Initiative in Infection and Immunity (MI4) and the McGill University Health Centre Foundation.
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Fabienne Landry
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