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Studies reveal how plague disables immune system, and how to exploit the process to make a vaccine

ecting the lungs rather than the bloodstream -- the disease is known as pneumonic plague. This form of the infection progresses faster, spreads easier from person to person, and is far more deadly, killing 100 percent of those who do not receive the right antibiotics soon after exposure. "There is," the authors note, "an urgent need for vaccine development."

One of this microbe's enduring mysteries has been how it gains a foothold in the host without triggering a protective immune response. In the Science Express paper, Schneewind and colleagues show how Y. pestis annihilates the first line of defense in the host's immune system before it can generate a full response.

The researchers infected mice with Y. pestis. Two to three days later they harvested cells from organs where the bacteria tend to cluster. They used a dye to stain those cells green.

When Y. pestis attacks a cell it uses the type-III pathway -- a needle-like projection -- to inject various toxins into the cell, killing it. The researchers endowed these bacteria with an additional enzyme, which the microbes also injected in cells. This enzyme can snip the green dye into two pieces. When that happens, those cells, when exposed to fluorescent light, glow blue instead of green.

This technique enabled the team to identify the cell types targeted by the bacteria. Two days after the mice were infected, their spleens were filled with bacteria. Although the overwhelming majority of immune cells in the spleen are B cells or T cells, nearly all of the infected cells were macrophages, neutrophils or dendritic cells.

These cells make up what immunologists call the "innate" immune system. They are the first to respond to a bacterial invasion. Their role is to rush to the infection site, engulf the bacteria, chew them up into smaller pieces and present those pieces to the T and B cells -- the "adaptive" immune system -- which enter the fray more slowly but bring powerful and ve
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Source:University of Chicago Medical Center


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