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Researchers discovered a previously unrecognized type 1 immune mechanism that preserves intestinal integrity in mice harboring tissue-invasive helminths.

A study published online in Cell revealed a previously unrecognized type 1 immune mechanism that preserves intestinal integrity in mice harboring tissue‑invasive intestinal worms, or “helminths”.

“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,” observed corresponding author Irah L. King, PhD, of the Research Institute of McGill University Health Centre in a news release. “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 defense. Our finding has broad implications, as it could potentially help fight various pathogens and diseases that cause intestinal damage.”

Rapid Induction of Interferon γ Signaling

According to the study, mice infected with tissue-invasive intestinal helminths showed a rapid induction of interferon γ (IFNγ) signaling. Although the interferon signals had no impact on the helminths, they signaled intestinal stromal cells to recruit neutrophils to limit tissue damage caused by the parasite. Gut motility was maintained through limited expansion of smooth muscle actin-expressing cells.

“Importantly, this tissue-protective response did not impact parasite burden, indicating that IFNγ supports a disease tolerance defense strategy,” researchers wrote.

Genetic Ablation Confirms Mechanism

Investigators confirmed their findings with genetic approaches that blocked intestinal stromal cells from receiving IFNγ signaling. In such cases, helminth infection resulted in intestinal bleeding and severe impairment of the digestive system, the team reported, highlighting the critical role IFNγ signaling plays in intestinal protection.

Clinical & Global Relevance

“What makes our research unique is that it looks at how the immune system functions within the architecture of the intestine itself,” said lead author Susan Westfall, PhD, of the Research Institute of McGill University Health Centre. “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.”

Future Directions

The team now aims to harness this stromal‑neutrophil circuit therapeutically—either by vaccine adjuvants that boost infection tolerance or by modulating stromal remodeling in malignancy, fibrosis, and chronic inflammatory bowel diseases. Their ongoing work may extend the principle of disease tolerance beyond parasitology into broad intestinal medicine.