Poorly understood cell plays role in immunity against the flu

A new understanding of a certain cell in the immune system may help guide scientists in creating better flu vaccines, report researchers from the Program in Cellular and Molecular Medicine and the Immune Disease Institute at Children's Hospital Boston (PCMM/IDI). Reporting online March 21 in Nature Immunology, they show, for the first time, that white blood cells known as resident dendritic cells (DCs) capture flu viruses and show them to B-lymphocytes, another white blood cell that recognizes germs and launches an antibody attack. Harnessing this previously unknown function could help activate the immune system more effectively against the flu virus. ...

Carroll's lab, in collaboration with Shannon Turley of the Department of Cancer Immunology and AIDS at Dana Farber Cancer Institute and Department of Pathology, Harvard Medical School, closely examined what happens when a flu vaccine is injected into mice, a good model for human vaccination. They focused specifically on what happens in the lymph node, where germs and vaccine antigens are filtered.

"We're trying to break down this black box that we know as the lymph node, and identify the different cells that are there, how they interact with each other and what the general rules are," Carroll says. "Then, you can begin to manipulate it to improve vaccines and immune responses."

When it comes to building permanent immunity, B-lymphocytes are the key players because they can remember specific germs and mount a rapid antibody attack. One way B-lymphocytes first encounter germs in the lymph nodes is through the help of macrophages, white blood cells that 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. ...

"This is the first clear definition of what the resident DCs are doing," Carroll says.  ... 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.  ...

via Poorly understood cell plays role in immunity against the flu.