Common parasite uncovers key culprit in Crohn's Disease
Immune systems have their sinister side, especially when they have not learned
how hard to fight. Inflammatory bowel diseases like Crohn’s disease inflict more
than a million Americans with debilitating pain and digestive unrest because of
uncontrolled immune responses in the gut.
How this happens remained a
mystery until immunologists at the Cornell University College of Veterinary
Medicine caught a key culprit in Crohn’s disease: a cell from our own immune
forces. With unconventional help from a common parasite, Dr. Eric Denkers and
Research Associate Dr. Charlotte Egan identified a renegade cell responsible for
this largely arcane and increasingly prevalent illness.
“Auto-immune
diseases are on the rise in this country but their causes have remained largely
unknown,” said Denkers. “It’s possible that these diseases are more common in
the West because we’re too clean. Exposure to germs trains immune systems how to
respond to threats. Early protection from germs may contribute to the increasing
prevalence of immune system overreactions in our population, leading to
auto-immune problems like allergies and inflammatory bowel
disease.”
Similar symptoms arise when some hosts first face the prevalent
protozoan Toxoplasma gondii. Denkers’ lab studies this parasite’s arsenal of
host-manipulating powers, but recently they have steered Toxoplasma research in
an entirely new direction.
“We noticed that the initial intestinal
inflammation these parasites can cause looks very similar to what happens during
Crohn’s disease,” said Denkers, one of the first to study this connection. “Our
lab has started using Toxoplasma to model Crohn’s Disease in humans and help us
find the pivotal perpetrator, which has turned out to be a cell from our own
immune forces.”
Specialized immune cells called intraepithelial
lymphocytes patrol intestinal walls (pictured above). Upon encountering
invaders, they release messenger proteins that call more immune cells to the
battle ground. “Too many messenger proteins recruit too many immune cells,
causing inflammation that can devastate the host’s own tissue,” Denkers
explained. “Bad balance between good bacteria, bad bacteria, and immune
interactions like inflammation cause Crohn’s disease.”
“For the first
time we’ve discovered how infection can turn these immune cells pathogenic,
stimulating them to cause disease, inflammation, and necrosis in the small
intestine,” explained Denkers. “This marks a major leap toward understanding
human Crohn’s disease. Unveiling this kind of immunological interplay may lead
to improved prevention and care in an array of auto-immune
diseases.”
Denkers and colleagues published their discovery in Mucosal
Immunology, followed by a review article discussing Toxoplasma infection as a
model for Crohn’s disease in the Journal of Biomedicine and Biotechnology in
2010.
Intestinal wall after Toxoplasma infection and subsequent immune system reaction resembling the effects of Crohn’s disease (left). Compare to an undamaged intestinal wall (right).
