Does diarrhea 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 diarrhea, concluding that it does play a critical role in
pathogen clearance in the early stages of infection. A new study also uncovers
a previously unrecognized role for interleukin-22, an immune system
molecule, in the host's defense against infection.
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 diarrhea. They found that
diarrhea resulting from the signaling 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 diarrhea is critical to enteric pathogen clearance, and that
IL-22 may play a key role in host defense.
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