New immune mechanism discovered to protect the gut
By studying intestinal worms, an international research team has achieved a breakthrough in the study of intestinal immunity. It could pave the way for better treatments for digestive disorders.
| Fabienne Landry, McGill University Health Centre
A research team from Canada, with the participation of Sebastian Weis’ group from the Leibniz-HKI and the University hospital in Jena, has discovered how the immune system protects the intestine during an infection with parasites – without fighting them. By studying intestinal worms, also known as helminths, the team was able to decipher a previously unknown immune mechanism that maintains intestinal function during a persistent infection.
“One of the ways our immune system protects us is by destroying viruses and bacteria. However, some pathogens, such as helminths, have found ways to evade destruction by our immune system. They can remain in the gut for months or years without causing disease,” explains Prof. Irah King, Senior Scientist in the Translational Research in Respiratory Diseases Program at the McGill University Health Centre in Montreal, Canada, and head of the study.
“Faced with this paradox, we investigated how the immune system tolerates helminth infection in the hope of uncovering the cellular pathways that mediate this form of host defense. Our findings have far-reaching implications as they could potentially help combat various pathogens and diseases that cause intestinal damage.”
Interferons play a fundamental role in protecting organ functions
Irah King’s team studied helminth infections in mice and discovered that they produce interferons – immune signals best known for their role in defending against bacterial or viral infections.
Surprisingly, however, the researchers found that they had no effect on the worms themselves. Instead, the interferons signaled the connective tissue cells – known as stromal cells – 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 that prevented stromal cells from receiving interferon signals. Under these conditions, the helminth infection caused intestinal bleeding and severe impairment of the digestive system, demonstrating the crucial role of interferon signaling in protecting the gut. “In the coming years, it will be interesting to explore whether the protective immune pathways we uncovered can be used in vaccines to promote infection tolerance or in therapies for inflammatory diseases such as cancer, inflammatory bowel disease and fibrosis, where uncontrolled activation of stromal cells leads to organ dysfunction,” says King.
The study was conducted under the direction of Irah L. King at the McGill University Health Center in Montreal, Canada. On the part of the Leibniz-HKI, the associated research group Translational Infection Medicine led by Sebastian Weis was involved in the research work. “We helped to analyze central cytokines, i.e. messenger substances, as well as organ damage markers that the Canadian team was unable to measure on site,” explains Weis. The researchers from Jena thus made a significant contribution to the functional classification of the immunological tolerance mechanisms to the worm infection.
The findings, recently published in the journal Cell, could pave the way for new treatments for helminth infections, which affect more than two billion people worldwide at some point in their lives, as well as other intestinal diseases. The findings could also help to rethink older therapeutic strategies that have so far been discarded due to an incomplete understanding of the biological processes involved.
Original publication
Westfall S, Gentile ME, Olsen TM, Karo-Atar D, Bogza A, Röstel F, Pardy RD, Mandato G, Fontes G, De’Broski H, Melichar HJ, Abadie V, Richer MJ, Vinh DC, Koenig JFE, Harrison OJ, Divangahi M, Weis S, Gregorieff A, King IL (2025) A type 1 immune-stromal cell network mediates disease tolerance and barrier protection against intestinal infection. Cell Vol. 188, Issue 12, Pages 3135-3151.e22, https://doi.org/10.1016/j.cell.2025.03.043
