A new study indicates how the immune system fights bacteria that cause the severe form of pneumonia known as Legionnaire's disease, Yale School of Medicine researchers report in the March issue of Nature Immunology.After infecting cells, the bacteria (Legionella pneumophila) can hide from the body's immune defenses by living and multiplying in sealed vacuoles inside cells. "The immune system detects bacterial products that leave the vacuole and activate 'suicide machinery' to eliminate the infected cell," said Craig Roy, associate professor in the Department of Microbial Pathogenesis and senior author of the study.
Roy and his colleagues report that the protein Birc 1e is important for the detection of Legionella infection. They pinpoint regions of Birc 1e that are needed to sound the alarm and show how Birc 1e activates components of the suicide machinery after infection with the Legionnaire's bacteria.
Using molecular and cellular assays, Dario Zamboni, a postdoctoral fellow and the lead author of the study, showed that Birc 1e interacts with Legionella and activates a signaling pathway that stimulates a protease called caspase-1. When the caspase-1 protease was activated, it degraded other cellular proteins, starting a cascade of events that resulted in cell death.
Cells from mice deficient in either the Birc 1e or caspase-1 protein allowed higher levels of Legionella replication, and these mice were more susceptible to disease following pulmonary infection.
"Identification of Birc 1e and the caspace cascade gives us information about the process of how the body fights off infection by a potentially lethal microbe, as well as possible targets for treatments," Roy said.
Legionnaire's disease received its name from a 1976 outbreak that occurred among people staying at a Philadelphia hotel that was hosting an American Legion convention. Later, the organism that caused the illness was named Legionella.
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