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Making flies sick reveals new role for growth factors in immunity
Date:10/23/2008

to excess cell growth during heart development, Dpp mutants also had an excess of plasmatocytes (blood cells involved in digesting small infectious particles) an important clue that Dpp was affecting the regulation of the immune system of the flies. Plasmatocytes are one of three types of immune cells that arise from hematopoietic stem cells embryonic cells that only take on their adult roles based on signals they receive from signaling molecules, including Dpp. However, how Dpp might specifically function in blood cell formation remained a mystery, and required fresh thinking.

With help from School of Life Sciences Professor Roy Curtiss, director of the Center for Infectious Diseases and Vaccinology at the Biodesign Institute at ASU, and his technician Bronwyn Gunn, Frandsen and Newfeld developed a novel experimental approach. Rather than curing their fly patients, they sought instead to make the Dpp mutants sick, hoping the infection with Salmonella would provide a new avenue to study their immune system defects in greater detail.

"The problem with the traditional approaches to studying immunity is that we keep our flies in a pretty clean lab they see few, if any, pesticides or parasites or anything they would need to defend themselves from," says Newfeld.

Getting flies sick wasn't trouble free, Frandsen says. At first, the fruit flies wouldn't eat the type of Salmonella that infects humans. But, with some clever cookery, a feeding technique was identified that led to Salmonella-infected flies. Once inside the flies, the Salmonella activated their immune systems. Newfeld points out that it was then that Frandsen made a key observation: Dpp mutant flies are unable to produce one type of immune cell that normal flies do in response to an attack by pathogens. This was the first piece of evidence that Dpp might regulate the options available to hematopoietic stem cells.

The lack of Dpp in fly mutants meant that their stem
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Contact: Margaret Coulombe
margaret.coulombe@earthlink.net
480-727-8934
Arizona State University
Source:Eurekalert

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