Grant: Operating Grant

Infections, particularly those that affect patients with compromised immunity like AIDS and those resistant to antibiotics, are among the most pressing challenges for mankind. It is not clear how we will defend ourselves against these ever increasing microbial invaders. The answer may lie in studies of the immune system. The information from these studies may provide new and exciting insights for therapies where antibiotics don't exist or where they have become ineffective. With this goal in mind, Dr. Mody's laboratory has been studying a class of cells that was originally identified because of their ability to kill tumor cells and cells infected with virus. Because of their ability to be toxic to, and kill other cells, they are called cytotoxic lymphocytes. Recently, it has been found that these cells can turn their attention to microbes like bacteria and fungi and kill these invading microbes. When they do, they are called microbicidal lymphocytes. Because this finding is so new, the mechanisms of recognition of the microbe, mechanisms of activation of the microbicidal lymphocytes and the killing mechanisms have not been well worked out. Imagine if this potent source of anti-infective cells could be harnessed and applied to therapy. Moreover, recent studies from Dr. Mody's laboratory demonstrate that this lymphocyte-mediated microbicidal response is defective in HIV-infected patients, and his laboratory is working to repair the defect. It is the goal of this proposal to study the normal and defective mechanisms with the purpose of providing new therapies for these challenging infections.