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Extremely infectious pneumonia-like disease slips through body's immune system

Published on December 21, 2005 at 10:37 PM · No Comments

A new study found that an extremely infectious pneumonia-like disease in humans slips through the immune system's usual defense mechanisms.

The bacterium at fault, Francisella tularensis, causes the disease tularemia. Also known as rabbit fever, tularemia is fatal in less than 1 percent of treated cases and in about 5 percent of untreated cases. It is a rare disease with only about 300 cases per year occurring in the United States .

But the disease can make many people very ill very fast, said Mark Wewers, the study's lead author and an assistant director of the Davis Heart and Lung Research Institute at Ohio State University. He and his colleagues report their findings in this week's online edition of the Proceedings of the National Academy of Sciences.

In this study the researchers found that, unlike other kinds of bacteria, Francisella is fully detected by the immune system only after it gets inside a monocyte, an immune cell whose job is to detect pathogens when they enter the body. Most pathogens are detected by sensors on the surface of monocytes, and these cells immediately respond by launching an attack.

However, monocytes don't immediately recognize Francisella as a threat because the bacteria can bypass those sensors. They cause a reaction only once they are inside the monocyte.

The fact that Francisella can spread so readily makes it an excellent possible weapon for bioterrorism, according to some experts.

"We estimate that if a terrorist dropped Francisella on a city it could make tens of thousands of people seriously ill," said Wewers, who is also a professor of molecular virology, immunology and medical genetics. "A widespread infection would put a lot of people out of commission for a long time."

During the Cold War, both the United States and the former U.S.S.R. stockpiled highly infectious strains of Francisella, Wewers said.

In North America , tularemia most commonly affects hunters and other outdoor enthusiasts. The bacterium is usually transmitted by ticks or by contact with an infected animal. Symptoms of tularemia can include high fever, swollen glands, throat infection, diarrhea and vomiting and large, reddish ulcers on the skin.

Understanding how the human immune system reacts to F. tularensis may help scientists to better comprehend how the body reacts to other infectious diseases, such as tuberculosis and the plague. This ultimately could lead to better treatments.

In laboratory experiments, the researchers infected human blood cells called monocytes with live cultures of Francisella novicida, a less-infectious form of Francisella. Monocytes are the "soldiers" at the immune system's frontline – these cells are the first to react when a pathogen enters the body.

The surface of a monocyte is dotted with structures called Toll-like receptors. These receptors function like barcode readers in that they scan for and determine the type of pathogen that has entered the body. The feedback that these receptors give the monocyte tells the cell how to react to the intruder.

Also on the surface of every monocyte is a tiny opening for a "sack" called a phagosome. Resembling a garbage bag, in a healthy immune system, the phagosome consumes disease-causing pathogens, eliminating them.

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