Immune regulation by passively acquired integral membrane proteins

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The prevention and clearance of infection and cancer requires a functional immune system with a well integrated immune response. The immune system uses a wide variety of mechanisms to maintain health and understanding how these immune functions are regulated is critical for the development of effective immune therapies and vaccines. We recently identified a novel method of communication among cells in the immune system. This communication occurs through the transfer of cell membranes and integral membrane proteins between immune cells and between cells in other organs and immune cells. This transfer of information occurs by a variety of mechanisms but conditions which result in inflammation, cell death, or cellular stress increases the release of membrane fragments by donor cells. This transfer of cell membranes and proteins can confer novel functions to the recipient immune cells. Our research focuses specifically on one type of immune cell, the neutrophil, as the recipient of cell membranes and integral membrane proteins. Neutrophils are the first cells recruited to sites of inflammation where there is ample opportunity to acquire membrane proteins being shed from a variety of cells. Neutrophils have an impressive capacity to rapidly acquire membrane proteins from necrotic and apoptotic cells and these acquired proteins can alter neutrophil function. The present research proposal will characterize the roles that neutrophils, which have acquired membranes from other cells, can play in regulating the development of immune responses. The mechanisms neutrophils use to transfer acquired information to other immune cells and regulate their responses will be determined. Understanding the regulation of immune responses by neutrophils will have direct application to improving vaccine design and may reveal novel strategies for the control of acute and chronic inflammation.