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Poorly understood cell plays role in immunity against the flu
Date:3/22/2010

hat trap germs and "show" them to B-lymphocytes. For this reason, some researchers believe macrophages to be a prime target in developing a vaccine. Carroll's lab designed their experiment to test this concept for the flu virus and got surprising results.

Working with a mouse model of influenza vaccination, the lab attached fluorescent labels to an inactivated strain of human H1N1 virus, allowing the inactivated flu virus to be tracked in the body. Imaging showed that macrophages trapped the virus in the lymph nodes and prevented most of it from entering the circulation. However, the macrophages did not bring the virus to B-lymphocytes, contrary to what was predicted. Instead, experiments which eliminated the macrophages from the mouse models showed that it was actually the resident DCs in the lymph nodes that were bringing the flu virus to the B-lymphocytes, thus inducing the B-lymphocytes to launch an antibody attack.

To confirm this observation, the researchers injected the mice with an agent to block a specific receptor on the surface of the resident DCs. With this receptor blocked, the B-lymphocytes never sprang into action. When it comes to the flu virus, these results suggest that any targeted vaccine must aim for resident DCs and not macrophages.

"This is the first clear definition of what the resident DCs are doing," Carroll says. The study adds to a growing body of research centered on DCs, which studies continue to show to play a role in stimulating other cells in the immune system.

Targeting influenza vaccines to DCs could make them more effective, Carroll believes. One hypothetical way of doing this would be to attach the virus to an antibody that would home in on the DC cell surface receptor. This method would require further research to confirm the antibody could actually bind to the DC receptor.

In the future, Carroll's lab would like to define a similar immune system pathway for Streptococcus pneumoniae
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Contact: Erin McColgan
erin.mccolgan@childrens.harvard.edu
617-919-3110
Children's Hospital Boston
Source:Eurekalert

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