Wellcome Sanger Institute research uncovers how parasitic whipworms are able to thrive in our guts
The human whipworm infects an estimated 500 million people globally, causing the neglected tropical disease trichuriasis.
The worm - Trichuris trichiura - has evolved over millennia to infect the intestines and reproduce there.
Wellcome Sanger Institute researchers and their collaborators have now identified the master regulator, known as the interleukin 10 receptor (IL-10R), that maintains a healthy gut and limits damage by parasitic whipworms.
In mice, a lack of IL-10R regulation led to an uncontrolled immune response that damaged the gut lining and led to a failure to produce protective mucus.
The worms invading the gut-lining cells destroyed the barrier between the gut and host, enabling bacteria to cross over into the rest of the body, causing fatal infection.
Dr Maria Duque-Correa, first author from the Wellcome Sanger Institute, said: “This work shows how any change in the host or microbiota will also change the response to whipworms. Interactions between the host cells, microbiota and whipworms enable the whipworms to survive in infected individuals and now we’ve found a master regulator of those interactions.”
Unravelling this signalling mechanism will help scientists understand immune response to other parasites and sheds light on pathways that could be involved in the control of other diseases, such as inflammatory bowel disease and allergies.
Prof Richard Grencis, an author from the University of Manchester, said: “This is the first study revealing the master role of IL-10R in regulating the response to whipworm, and controlling the microbiota. We discovered the absence of this crucial signalling pathway leads to disturbed microbiota and uncontrolled inflammation that destroys the gut lining allowing microbes to invade and cause liver failure.”
Dr Matt Berriman, senior author from the Wellcome Sanger Institute, said: “Our discovery of the importance of the IL-10R signalling pathway for gut regulation not only helps us understand the immune response to parasites, it also has implications for other diseases.
“Further research to better understand this immune signalling pathway could open up new ways of finding treatments for diseases caused by an overactive immune system such as allergies, inflammatory bowel disease or asthma.”
The study was published in PLOS Pathogens.