Research led by Neal S. Silverman, PhD, and published in Molecular Cell, sheds new light on the process the immune system uses to rapidly and robustly produce antimicrobial proteins to fight off infection.
While receptors on immune cells are known to recognize bacterial microbes, the precise molecular mechanism leading to activation of genes that produce antimicrobial bodies and other immune responses is unclear. To understand these processes better, Silverman and his colleagues examined how one of the principal regulators of the immune system, the IMD pathway, works to activate the immune system in Drosophila. What they found was that recognition of DAP-type peptidoglycan (PGN), a molecule found in most gram-negative bacteria such as E. coli, initiated three molecular mechanisms that collectively are essential for activation of the immune system and antimicrobial genes.
“These immune responses are critical for immediate protection against bacterial infection in Drosophila,” said Silverman, associate professor of medicine and molecular genetics & microbiology. “Better understanding of the molecular process taking place in Drosophila provides clues to what happens in our immune system and points to the existence of an unidentified protein that may play a similar role in humans.”
This cascade of events observed by Silverman and colleagues begins when the presence of gram-negative bacteria is detected. As a result of the bacteria’s presence, the IMD protein cleaved, exposing a binding site on the IMD molecule allowing it to adhere to an IAP molecule. Once docked with the IAP protein, the IMD protein is rapidly activated, triggering production of antimicrobials and immune protection.
“By identifying how the IAP molecule binds to the IMD protein and the role it plays in activation of the immune system, it is possible that if a similar process is involved in humans, novel agents can be developed to inhibit or intensify the response of the immune system,” said Silverman. “This could have implications in developing new drug targets for autoimmune diseases or augmenting the body’s natural response to bacteria infection.”
The next step for researchers is to identify a similar pathway in animals.
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