New study overturns orthodoxy on how macrophages kil...( CHAMPAIGN Ill. For decades microbio...)

CHAMPAIGN, Ill. For decades, microbiologists assumed that macrophages, immune cells that can engulf and poison bacteria and other pathogens, killed microbes by damaging their DNA. A new study from the University of Illinois disproves that.

The study, published in the journal PLoS ONE, shows that macrophages focus their most potent poisons, known as reactive oxygen species (ROS), on targets outside the cytoplasm.

Macrophages are voracious eaters that "swallow" cellular debris and invading organisms. They kill microbes with ROS. All aerobic cells inadvertently produce ROS that can, if left unchecked, damage DNA and other cellular components and cause cell death.

Bacteria and animal cells contain special enzymes, called superoxide dismutases, which neutralize an important ROS, called superoxide.

Macrophages have harnessed these lethal compounds, dumping large quantities of superoxide onto engulfed bacteria to kill them.

Although macrophages direct ROS against invading bacteria, Salmonella typhimurium, the microbe used in the study, is adept at evading these defenses. The most virulent strains of S. typhimurium can survive and even propagate inside macrophages, eventually emerging to infect more cells.

"It's been assumed that reactive oxygen species kill the bacteria by going into the cytoplasm and causing DNA damage," said medical microbiology professor James Slauch, who led the study. "You can find this idea over and over again in review articles and many immunological textbooks, but with no real data to back it up."

To test this hypothesis, Slauch and graduate student Maureen Craig looked at the superoxide dismutases that are part of the bacterial defense against ROS. There are two such enzymes in the cytoplasm of S. typhimurium, called SodA and SodB, and another, SodC, in the periplasm, the space between the bacteria's inner and outer membranes.

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