Tales from the crypts: Cells battle germs

Consider them the guardian angels of your small intestine.

Long known as Paneth cells, these sentries inhabit tiny pits in the intestine called crypts. Scientists now offer the best evidence yet that these cells defend other cells in the crypts by discharging bacteria-killing bursts of enzymes and other molecules.

Protecting the crypt’s so-called stem cells, which replenish the lining of the small intestine, is vital. With a surface area about the size of a football field, the lining is continually damaged by digestive enzymes and bile. It must therefore turn over rapidly, every few days in a person.

It’s up to the stem cells, which dwell just above the Paneth cells, to spawn progeny that migrate onto the tips of fingerlike villi that line the intestine and absorb nutrients.

For years, scientists have amassed a case that Paneth cells safeguard stem cells. They initially found that Paneth cells contain stores of lysozyme, an enzyme that breaks down bacterial cell walls. More recently, they documented similar accumulations of defensins, small proteins with antimicrobial powers. Still, it remained unclear whether Paneth cells use these as weapons to destroy germs.

Andre J. Ouellette of the University of California, Irvine and his colleagues had hoped to study Paneth cells by growing them in petri dishes, but the cells failed to thrive. The investigators instead used intestinal tissue from mice and exposed the tissue’s intact crypts to various microbes and microbial molecules. Bacteria, including the food-poisoning culprits Escherichia coli and Salmonella typhimurium, trigger the Paneth cells to secrete large amounts of defensins and other molecules, the researchers report in the August Nature Immunology.

The work of Ouellette and his colleagues “is a successful culmination of efforts to understand Paneth cell function,” comments Tomas Ganz of the University of California, Los Angeles in the same journal. “They determine that Paneth cells are the sentinels of crypts: they react to bacteria by releasing defensins in more than sufficient quantity to kill.”

While Paneth cells appear to protect crypts from bacteria, biologists still must investigate whether the cells’ sterilizing power extends into the general cavity of the small intestine. Full of nutrients that an animal is trying to absorb, the small intestine would seem to offer a pleasant home to bacteria and other microorganisms. Yet compared with the colon, the small intestine harbors significantly fewer microbes.

Paneth cells may be the reason, suggests Charles Bevins of the Cleveland Clinic Foundation. He notes that biologists are also investigating whether problems with Paneth cells lead to inflammatory diseases within the small intestine.

Ouellette’s team is now trying to identify the bacteria-detecting surface molecules on Paneth cells. The researchers will also examine why their initial experiments found that Paneth cells don’t react to fungi or other nonbacterial microbes.

“We’ve just started to look at the responses of these cells,” notes Donald P. Satchell, one of the study’s authors.