Just like spiders, we weave webs ? microscopic ones that capture and prevent microbes from irritating the lining of the small intestine. This discovery could help with the development of treatments for inflammatory bowel disease.
"We think their major function is to defend against fungi, bacteria and other pathogens," says Charles Bevins, head of the team at the University of California, Davis, that discovered the webs.
The protein that makes this intestinal web ? human alpha defensin 6 (HD6) ? has been a mystery for decades. HD6 was thought to kill invaders directly, by punching holes in the walls of bacteria, for example, because that is how other defensins such as HD5 work.
Yet when Bevin's team tested HD6 against bacteria, it didn't seem to kill them. Then, three years ago, one of his graduate students, Hiutung Chu, noticed that a white web-like haze formed when she added HD6 to a solution containing fungi. "That was the eureka moment, when the penny dropped with what was going on," says Bevins.
Caught in a trap
Further investigation showed how, in the right environment, HD6 molecules bind to each other to form a fibrous web after they have ensnared individual bacterial or fungal cells. This web prevents trespassers from infiltrating intestinal crypts ? recesses that lie at the bottom of villi that line the small intestine.
These crypts are the factories where stem cells regenerate the lining of the gut about every three days. "Anything that gets into the crypt is a potential threat to this process, and that's why it's so well protected," says Bevins.
The webs trap all alien cells, whether friend or foe, because as the gut's new cell factory, the crypt is essentially a no-go area. Once enmeshed in the webs, bacteria or fungi are thought to be flushed away from the gut wall by a release of fluid from cells at the base of the crypts.
Bevins says that HD6 and its more pugnacious counterpart, HD5, are found at abnormally low levels in people with inflammatory bowel diseases, particularly in those with Crohn's disease affecting the final part of the small intestine ? the ilium. This suggests that a decreased level of crypt protection may be a contributing factor.
He and his colleagues are now trying to establish how HD6 distinguishes invading cells from host cells, which could lead to new treatments for inflammatory bowel disease.
"What a great strategy to prevent microbes from attaching to the gut surface," says Michael Zasloff, a surgical immunologist at Georgetown University Hospital in Washington DC. "It's a wonderful discovery."
Journal reference: Science, DOI: 10.1126/science.1218831
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