The immune master regulator orchestrates responses to parasitic infection

A new study has identified the main regulator that maintains a healthy gut and limits the damage caused by parasitic badworms. Researchers at the Wellcome Sanger Institute and collaborators have revealed that the interleukin-10 receptor (IL-10R) is essential to prevent uncontrolled infection by badworm in mice and a damaging immune response to the disease. 39; intestine.

The study, published today (31 January) in PLOS Pathogens, helps to understand the signaling mechanism that maintains a balance between host, badworm and intestinal bacteria. The discovery of this signaling mechanism will help scientists understand the immune response to other parasites and will better understand the pathways that might be involved in the control of other diseases such as inflammatory diseases of the body. 39, bowel and allergies.

The intestine hosts millions of bacteria, called microbiota, as well as parasites such as badwigs. The human badworm – Trichuris trichiura – Infects about 500 million people worldwide, causing the neglected tropical disease, Trichuriasis, and has evolved over millennia to infect the intestines and reproduce there.

Host health is important for a parasite because it needs a live host to survive and reproduce. The researchers found that the worm, intestines, immune system and microbiota form a finely balanced ecosystem.

Dr. Maria Duque-Correa, first author of the Wellcome Sanger Institute, said, "This work shows how any change in the host or microbiota will also alter the response to badworm worms, to survive in infected individuals and now we found a master regulator of these interactions ".

Some immune signaling molecules, called interleukins, had previously been implicated in the host's immune response to worm infection, regulating inflammation in the intestine. To better understand their role in this balanced ecosystem, researchers studied gene-free mice in the interleukin 10 receptor superfamily (IL-10) to determine their response to badworm infection. .

The researchers discovered that a specific receptor for IL-10R was essential to regulation. They found that the lack of regulation of IL-10R resulted in an uncontrolled immune response that damaged the intestinal lining and did not produce protective mucus. The worms invade the cells of the intestine, destroy the barrier between the intestine and the host, allowing the bacteria to enter the rest of the body, causing a deadly infection.

Professor Richard Grencis, author at the University of Manchester, said: "This is the first study revealing the main role of IL-10R in regulating the badworm response and Microbiota control We have discovered the absence of this crucial microbiota signaling pathway disrupted and uncontrolled inflammation that destroys the intestinal mucosa, allowing microbes to invade and cause liver failure. "

Dr. Matt Berriman, lead author of the Wellcome Sanger Institute, said, "Our discovery of the importance of the IL-10R signaling pathway for intestinal regulation not only helps us understand the immune response to parasites, but also to other diseases.Additional research to better understand this immune signaling pathway could open new avenues for finding treatments for diseases caused by a hyperactive immune system, such as allergies, inflammatory diseases of the body, and other diseases. bowel or asthma. "

Provided by
Wellcome Trust Sanger Institute