Researchers identify pathogen-specific gene response in human im...( o three common pathogens: a virus (infl...)

o three common pathogens: a virus (influenza), a bacterium (Escherichia coli), and a fungus (Candida albicans). They looked for genes that were turned on or off in a dendritic cell after it encountered a pathogen, thus generating a snapshot of which genes were active during a dendritic cells response to a specific pathogen.

Several clear results emerged from these studies. First, dendritic cells were able to activate genes that regulate several phases of the immune response from the early and rapid defenses (neutrophils and macrophages) to the later, long-lived, and potent responses (T and B cells). Second, pathogens were able to guide activation of these dendritic cell genes, so that only particular arms of the immune response were induced by a pathogen. For example, E. coli was able to rapidly induce a set of genes that attracts neutrophils; however influenza virus was not able to activate these genes. These kind of results allowed the authors to conclude that the dendritic cell plays an important role as a messenger in the bodyit senses infections in the bodys tissues and carries instructions to the immune system to activate its different arms.

Hacohen says that only a small fraction of the identified genes may become targets for therapy, but that the larger set of genes does provide clues to finding the key players, or group of genes, involved in the tussle between the microbe and the immune cell. The most important task right now is to determine whether the responding genes are most beneficial to the life of the host or the pathogen.

"In this study, we have identified a large set of genes that are activated in the presence of pathogens. The next step is to determine what specific function those genes have in dendritic cells," says Hacohen. "In addition, we can now ask more meaningful questions about how these genetic programs get turned on and off, and use those insights to design better therapies."

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Contact: Melissa Withers
withers@wi.mit.edu
617-258-7403
Whitehead Institute for Biomedical Research
25-Oct-2001

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