Scientists have revealed a crucial mechanism used by the immune system to shield the gut during an infection. This work, which used a mouse model of intestinal worm infections, showed that the immune system can preserve the normal function of the intestine even when a persistent infection is happening. The study, which was reported in Cell, could reveal more about how to treat gastrointestinal infections. It also raises new questions about old therapeutic approaches that were once dismissed, potentially because of an inadequate understanding of biology.
"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," noted senior study author Professor Irah King, Ph.D., a Senior Scientist at the Research Institute of the McGill University Health Center (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 defense. Our finding has broad implications as it could potentially help fight various pathogens and diseases that cause intestinal damage."
Parasitic worms called helminths are estimated to infect about 2 billion people at some point during their lifetimes. In this work, the researchers assessed helminth infections in a mouse model, and determined that immune signaling molecules called interferons are generated during helminth infections. Inteferons are known to be produced during bacterial and viral illnesses.
But the interferons, surprisingly, were not combating the helminths; they had no impact on the parasites. The interferons were signaling to cells called stroma, which affect organ shape and structure, to control damage that was happening due to the helminths, and protect the normal function of the intestine.
When the researchers stopped the stroma from receiving these signals (with genetic tools), the intestine was severely disrupted, and intestinal bleeding started. The interferons, therefore, seem to be performing a crucial protective role.
The intestine is often damaged by infections or chronic inflammation that can arise because of dietary factors, pollution, or other environmental factors. Intestinal infections are a common problem, worldwide. This research has revealed one way that the intestine can be shielded from damage.
"The scientific and medical communities are struggling to find ways to treat intestinal damage without resorting to major surgery or aggressive medications," said first study author Susan Westfall, a postdoctoral fellow in the King lab.
The investigators noted that it's not only important to understand how infections happen and how to get rid of them; but we also have to investigate what happens during an infection, and what long-term damage might arise.
"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," added King.
Sources: McGill University, Cell