1 min readResearchers Explore Immune Mechanism that Drives Diarrhoea and Its Role in Clearing Infections

Boston, MA — Researchers want to know: does diarrhoea serve a purpose? Does it actually help clear the bacteria causing a gastrointestinal infection, or is it merely a symptom of disease that should be prevented as much as possible?

In a new study from Brigham and Women’s Hospital, investigators explore the immune mechanism that drives diarrhoea, concluding that it does play a critical role in pathogen clearance in the early stages of infection. The new study, published today in Cell Host and Microbe, also uncovers a previously unrecognized role for interleukin-22, an immune system molecule, in the host’s defence against infection.

“The hypothesis that diarrhoea clears intestinal pathogens has been debated for centuries,” said corresponding author Dr. Jerrold Turner, of the BWH Departments of Pathology and Medicine. “Its impact on the progression of intestinal infections remains poorly understood. We sought to define the role of diarrhoea and to see if preventing it might actually delay pathogen clearance and prolong disease.”

To investigate, researchers used a mouse model infected with Citrobacter rodentium, the mouse equivalent of an E. coli infection. Using this model, they saw an increase in the permeability of the intestinal barrier within just two days of infection — well before inflammation and epithelial damage. In particular, they uncovered a critical role for interleukin-22 that in turn influences another molecule called claudin-2, previously known to be involved in causing diarrhoea. They found that diarrhoea resulting from the signalling of these two molecules helped promote pathogen clearance and limited disease severity.

Other investigators have proposed developing new therapeutics to inhibit claudin-2. However, Turner and colleagues explain that the activation of this pathway may be critical for combating an infection, particularly in the early stages of a disease. They conclude that diarrhoea is critical to enteric pathogen clearance, and that IL-22 may play a key role in host defence.

Article adapted from a Brigham and Women’s Hospital news release.

Publication: IL-22 Upregulates Epithelial Claudin-2 to Drive Diarrhea and Enteric Pathogen Clearance. Pei-Yun Tsai et al. Cell Host & Microbe (2017): Click here to view.

Medical Microbiology

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