Scientists determine how the body counteracts anthrax attacks

Scientists at the University of California - San Diego School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences have released findings about how the body’s immune system counteracts anthrax attacks.

The anthrax bacterium can often begin a deadly response that invades immune cells called macrophages and releases potent toxins to paralyze important biochemical pathways and cause rapid cell death. If unchecked, the process can lead to a complete collapse of the body’s immune defenses and eventually septic shock and high mortality.

The researchers found that once macrophages are impacted, they communicate with other immune cells to sound the alarm and develop a survival strategy. The signaling molecule in the survival response is adenosine triphosphate, the basic currency of energy transfer used by all organisms.

"The warning alarm sounded during anthrax infection is elegant, complex and can be effective in slowing spread of the pathogen," Michael Karin, a professor of pharmacology and the senior author of the study, said.

Once the infected macrophage’s warning signal is sensed on a second macrophage, the second macrophage assembles and activates a complex of molecules called the inflammasome. The inflammasome releases the immune-activating molecule called interleukin-1beta, which alerts other macrophages to mobilize and increase resistance to anthrax-induced cell death.

The researchers found that if they altered the ATP channel, the ATP receptor, inflammasome proteins or the IL-1beta molecule, the macrophages could not survive, anthrax bacteria grew unchecked or the infected mouse died rapidly. This particular immune response pathway only occurred with the most dangerous bacterial pathogens.

"We hope these findings can be exploited for the design of new treatments to help the body combat serious bacterial pathogens," Victor Nizet, a professor of pediatrics and pharmacy and a contributor to the study, said. "Supporting the survival of macrophages and preserving their immune function may buy patients precious time until antibiotic therapy is brought on board to clear the infection."