Allergy-Producing Cells Are Also "Do-Gooders," Helping Stave Off Infections

The researchers say the discovery, which appears in the July 6 issue of the Proceedings of the National Academy of Science, may lead to new ways to fight infections, particularly in patients whose immune systems are compromised during an organ transplant or HIV infection.

The research is supported by grants from the National Institutes of Health and the Medical Research Council.

"For years people have wondered why we have mast cells when they seem to do nothing but cause misery for people with allergy and asthma," said microbiologist Soman Abraham, lead investigator of the study. "Now we've shown that the mast cell has a crucial role in identifying potentially dangerous bacteria and alerting the immune system to destroy them."

The much maligned mast cells lie just beneath the surface of virtually all body tissues that have contact with the outside world: the skin, gut, nasal passages, lung and urinary tract. For years mast cells seemed only to be a sort of cry-wolf cell that overreact to the inhalation of substances as benign as pollen grains and release a flood of inflammatory molecules and histamine - the bane of allergy sufferers.

But Abraham and his colleagues discovered a more subtle but powerful role for mast cells. The researchers found a molecule called CD48 on the mast cell surface. CD48 recognizes a protein called FimH on the tips of hair-like projections on many infectious bacteria. This CD48-FimH connection triggers mast cells to alert the immune system by releasing a substance called tumor necrosis factor alpha (TNF-a), which is a type of early warning system of infection, Abraham said.

"We are bombarded with bacteria every day," Abraham said. "In healthy people, mast cells seem to help clear the body of bacteria quickly, so that you don't even know you've been infected. Only when you get such a huge dose of bacteria that the mast cells can't cope or when your immune system is compromised do the bacteria gain a foothold."

Typically, mast cells are not activated by the beneficial bacteria that inhabit the gut, because such bacteria colonize the surface of the intestinal lining, he said. Only when bacteria become invasive, burrowing into the gut lining, are the mast cells alerted.

The Duke scientists' discovery also appears to clear up a mystery about the function of the CD48 protein. Although CD48 was discovered more than 10 years ago as a protein that appears on the surface of some white blood cells such as mast cells, its biological role has not been clearly defined.

In their experiments, Abraham and his colleagues showed that antibodies to CD48 blocked mast cells from recognizing bacteria and stopped the mast cells from releasing the signaling molecule TNF-a in the presence of bacteria. This finding led the researchers to conclude that CD48 is a specific receptor on mast cells that recognizes bacteria and triggers the release of TNF-a, which alerts the immune system to destroy the bacteria.

The researchers will now try to find ways to beef up the mast cells' ability to fight bacteria in people with weakened immune systems, such as people infected by HIV or who are taking anti-rejection drugs following organ transplantation. Such a strategy might be a way to avoid overuse of traditional antibiotic treatment, said Abraham.

"Now that we know that CD48 is the important trigger, we can target treatments that would trip that trigger to help boost the immune system's ability to fight infection in people with immune deficiency," he added.

Ravi Malaviya, Zhimin Gao, Krishnan Thankavel and P. Anton van der Merwe also contributed to the research.