Hamilton scientist finds key to body’s immune system

What happens in moments after flesh-eating bacteria invades the body can best be described as bizarre.

The bacteria — caused by the same Streptococcus pyogenes that causes strep throat — tells the body’s front-line immune system cells to kill themselves.

By JENNIFER McKEE
Gazette State Bureau

And they obey.

"I was surprised," said Frank De Leo, a scientist at Rocky Mountain Laboratories who headed the team of Montana scientists who discovered strep’s subversion strategy and shed new light on how the body’s immune system works. Their study will be published in this week in the journal "Proceedings of the National Academy of Sciences."

The group’s discoveries were lauded as a "work of seminal importance," by Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, which oversees Rocky Mountain Labs.

It’s not just the unexpected activities of strep that caught the attention of the science world, said William Nauseef, a University of Iowa expert on inflammation. De Leo’s work turns on its head the traditional view of the immune system as a troop of disease-killing soldiers, armed with everything they need to wipe out invading bacteria. De Leo’s work shows that the immune system actually relies on the uncanny ability of its most common cells to invent totally new defenses in the thick of battle to literally transform each cell to match the abilities of the invaders. De Leo showed that up to 600 genes inside each immune system cell are activated as they take on invading pathogens — evidence that the cells themselves change to defeat an enemy.

"We didn’t really appreciate that before," Nauseef said.

De Leo and his group looked specifically at a kind of cell called a neutrophil. At any given time, De Leo said, millions of neutrophils are rambling around a person’s blood stream, destroying bacteria and dying slow, controlled deaths. Neutrophils are some of the most common cells of the immune system, but they have not been studied extensively. De Leo estimates that about 200 scientists nationwide specialize in neutrophils. Among them are the five people in his Hamilton lab.

Neutrophils are "the cells that make up pus," Nauseef said.

They are the first to arrive when any new pathogen enters the body and they have a powerful weapon. They make the main ingredient in household bleach.

"So, they’re very effective at killing bacteria," De Leo said.

But they don’t just kill bacteria. Neutrophils also kill themselves. Constantly. Whether they’re taking down the bacteria behind relapsing fever or just existing in the blood stream, neutrophils last only a few days in the body. The immune system is always churning out millions of new ones.

Science has long known what neutrophils do, he said, and it was also common knowledge that neutrophils die a lot. (If neutrophils didn’t die after wiping out an infection, there’d be a lot more pus and inflammation in the world. In fact, the failure of neutrophils to die is behind a host of common ailments, including arthritis.)

About a year and a half ago, De Leo posed the question: Just exactly how do they work and how do they die? Most cells die by exploding. But if neutrophils exploded, they’d release their arsenal of bleach and actually cause more tissue damage than infecting bacteria.

To find the answer, De Leo and the folks in his lab inserted various pathogens into drops of pure neutrophils and then studied all the genes in the cell. What they found is that hundreds of genes "turn on" in the thick of battle. At the end of the battle, a certain set of genes activate that tell the cells to quietly and efficiently die.

Then things got weird.

They discovered that strep targets those self-destruction genes. Under the influence of strep, neutrophils died faster, randomly, even exploding and releasing their bleach-like weapons.

"That actually helps spread the bacteria around," De Leo said.

Their research also left them with a good follow-up question: Exactly how does strep command human genes?

"That’s the next research," De Leo said.

Copyright © The Billings Gazette, a division of Lee Enterprises.

http://www.billingsgazette.com/index.php?id=1&display=rednews/2003/09/03/build/local/60-immune.inc

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Research team is Montana through and through

By JENNIFER McKEE – IR State Bureau

HAMILTON — Frank De Leo’s laboratory is notable for another reason — it’s made up entirely of Montanans.

Every member of the five-person team that recently revealed how a key element of the immune system works — or doesn’t work in the case of sneaky strep bacteria — is either from Montana, a graduate of a Montana university, or both.

Scott Kobayaski, one of the researchers, said he knows of only one other lab at Rocky Mountain Laboratories in Hamilton with such a high saturation of Montanans. Kobayaski is from St. Louis, Mo., originally but graduated from Montana State University in Bozeman.

De Leo grew up on a ranch outside of Helena, graduated from high school in Seeley Lake and earned his doctorate from MSU-Bozeman. Now a father of two small children, De Leo returned to Montana in 2000. He was drawn here, he said, not so much to be close to home, but because Rocky Mountain Labs offered the kind of work he wanted to do.

De Leo, who did all the hiring for his lab, said he didn’t go looking for Montanans.

http://helenair.com/articles/2003/09/03/montana/a01090303_06.txt