Anthrax attack. One of Bacillus anthracis's toxins paralyzes dendritic cells.

Anthrax's Lethal Knockout

A toxin produced by the anthrax microbe knocks out the first line of defense in an animal's immune system, possibly allowing the bugs to replicate unchecked, according to a paper published in the 17 July issue of Nature.

Bacillus anthracis can very rapidly kill people and animals, thanks in part to two toxins known as edema toxin (ET) and lethal toxin (LT). Until now, scientists knew more about the role of ET, a protein that causes redness and swelling of the skin and other organs. Recent work had shown that LT can kill macrophages, a class of immune cells that gobble up bacteria. Now, a study suggests that it may also have a subtle but nefarious effect on another class of cells called dendritic cells.

Patrolling the bloodstream, dendritic cells normally act as sentinels that signal specific T cells to come fight off foreign microbes or pathogens. But the LT toxin can prevent dendritic cells from doing their job, the new research shows. In a series of experiments in which they either added LT to dendritic cells in vitro or injected LT-exposed dendritic cells into mice, a team led by immunologist Bali Pulendran of Emory Vaccine Research Center in Atlanta found that the cells became "lethargic," Pulendran says. Additional studies by the team suggested that the toxin blocks a vital signaling route called the MAP kinase pathway within the dendritic cells. Silencing the immune system may give the bacteria unbridled opportunities for growth, the authors note. In the future, they speculate, specific drugs to block LT may help anthrax patients better fight the disease.

Although LT's new role is "exciting to contemplate," says Harvard immunologist Michael Starnbach, it's hard to see why the bacteria would need it. T cell activation by dendritic cells takes a long time, he says; anthrax kills so fast that it's questionable whether the microbes would even profit from blocking this system. "A patient might be dead before it's important," Starnbach says.

Related sites
Bali Pulendran's laboratory Web site at the Emory Vaccine Center
The Centers for Disease Control and Prevention's anthrax Web site