Until recently, very little was known about the biological factors that make anthrax, a pathogen that normally strikes livestock and wild animals, cause lethal infection in humans. NIEHS-supported researchers have discovered that anthrax produces a deadly toxin that prevents the immune system from recognizing and fighting the infection. These findings may lead to the development of an antidote that could block the action of the toxin, giving the immune system time to detect the infection and fight it.
When anthrax is inhaled, the spores are surrounded by macrophages, large white blood cells that serve as the body’s first line of defense against pathogens. Instead of succumbing to this assault, the bacteria survive and reproduce within the white cells. They eventually invade the lymph nodes and enter the blood stream, causing widespread infection, disease and death. Although anthrax is a naturally occurring, recent attention has focused on its use as a biological weapon. The most lethal form of anthrax infection results from inhalation of spores containing the rod-shaped bacterium Bacillus anthracis.
Tests conducted in mouse macrophage cells by NIEHS grantees at the University of California at San Diego show that the anthrax bacteria produce a toxin called lethal factor that disables a key protein necessary for normal immune function. Loss of this protein results in the death of the macrophages and prevents the secretion of chemicals that alert the immune system to the presence of an invading pathogen. This allows the bacteria to escape detection and spread throughout the body.
The results of these studies may explain why many anthrax infections go undetected until the patient is very sick and near death. These findings may also lead to the development of specific antidotes that can block the action of the lethal factor toxin. Future research will focus on the delicate balance required for macrophage survival, since these cells play a crucial role in the pathogenesis of anthrax and other deadly infections.