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Killer Cells Get a Boost

1 July 2005 (All day)
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Immune warrior. Mice lacking HIF-1 (right) have a harder time fighting infection than those that express the protein.

White blood cells help our bodies fight infection by killing harmful bacteria. Now researchers have discovered how these cells turn their weapons on and off. The findings may give doctors a powerful new tool for boosting a patient's immune system.

White blood cells have a high-stress job. Infected tissues teem with dangerous bacteria that drive down oxygen levels by destroying surrounding blood vessels. When the cells reach the bacteria, they attack them with antimicrobial compounds like nitric oxide and cathelicidins--proteins that poke holes in bacterial membranes.

But white blood cells don't need to make killer compounds all the time. Otherwise they might destroy good cells while wasting precious energy. So biologist Carole Peyssonnaux, microbiologist Victor Nizet, and colleagues at the University of California, San Diego, investigated how the cells might regulate their protective behavior. The researchers found that, in mice, white blood cells make a protein called HIF-1 that revs up the production of antibacterial compounds when oxygen levels begin to drop, or when the cell encounters a harmful bacterium. In contrast, HIF-1's activity is reduced when the cells are circulating through the oxygen-rich blood stream.

To determine HIF-1's role in fighting infection, the team engineered mice that were incapable of producing the protein in their white blood cells. Compared to normal mice, mice without HIF-1 had 1000 times more bacteria in their body post-infection and developed skin legions that were twice as big, the team reports today in the Journal of Clinical Investigation.

"Turning on HIF-1 is like a white blood cell pulling out its sword as it enters infected tissue," says Nizet. If the protein works the same way in humans, he notes, it may be possible to augment the body's natural infection fighting abilities. As opposed to using medicine as an antibiotic, he says, we might one day have a pill that increases the levels of HIF-1 in white blood cells.

The authors are the first to show how HIF-1 regulates a white blood cell's bacteria-fighting abilities, says microbiologist Kol Zarember, a research fellow at the National Institutes of Health. "This demonstrates a very important mechanism for boosting the immune system."

Related sites
The study
Johnson Lab site
Nizet Lab site

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