Rare white blood cells employ novel methods to destroy bacteria in the gut

Monday, August 25, 2008

SCOTTSDALE, Ariz. - The gut, the body's gastrointestinal (GI) tract, may have a potent new ally, and it doesn't come in the form of a pill or a soothing minty liquid.

Eosinophils, white blood cells generally linked with defense against parasites and allergies such as asthma, are earning renewed respect as a novel weapon the body uses to fight bacterial infection.

Research published online this month in the journal, Nature Medicine, suggests that eosinophils use DNA (the hereditary material that encodes genes) in a very unorthodox way: Eosinophils locate bacteria and then hurl DNA and toxic proteins at them, creating a powerful entanglement of DNA and protein that immobilizes and kills bacteria. This finding suggests that the intestinal tract utilizes many unconventional approaches to maintain a barrier against marauding harmful bacteria.

James Lee, Ph.D., a Mayo Clinic researcher and co-author of the study, said that these observations are unique for two reasons: "First, eosinophils are an extremely rare white blood cell (less than 1 percent of all white blood cells) that release a series of toxic proteins suspected in the cellular death surrounding parasite infections and the lung damage occurring in asthmatics." Adds Lee, "More importantly, they generally are not thought of as a bodily defense against bacteria. Instead, that job was suggested to fall to another white blood cell, the neutrophil, which comprises nearly 40 percent of all the white cells."

Secondly, Lee says, all cells in human bodies, including eosinophils, contain little organs (organelles) called mitochondria that produce energy. "The mitochondria are so complex that they need to carry with them their own genetic information to encode this structure. Surprisingly, it is this DNA that the eosinophils catapult out at the bacteria in rapid-fire fashion – a very odd use of genetic material. It's like throwing a phone at a criminal instead of calling the cops."

What is gaining attention, Lee explains, is that because eosinophils normally reside in the gut right at the barrier where the intestinal bacteria live, this strategy of throwing a DNA-toxic protein net may be a "crude but effective means with which to control the growth of bacteria, and may be critical for both maintaining health and fighting disease."

The intriguing finding for researchers is that many other gut-associated diseases may also involve eosinophils and their potential defensive roles. For example, eosinophils and the release of their toxic proteins is a prominent feature of inflammatory bowel diseases, such as Crohn's disease. Symptoms in an animal model of this gut disease appear to be responsive to treatments directed at eosinophils.

Lee says he has seen remarkable changes in the way medicine looks at eosinophils. "When we started out, eosinophils were the odd-cell-out among the white cells. They were thought of as a minor destructive cell population of limited use. Instead, they now appear to be versatile cells with multiple functions in an ever increasing number of diseases."

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