The plan of this research is to identify the receptors on macrophages which are involved in the phagocytosis of leishmania promastigotes. Our hypothesis is that the initial binding mechanism determines the parasites' intracellular fate. We have identified two different mechanisms by which macrophages bind leishmania (types I & II), and have preliminary evidence identifying the macrophage receptors involved in each. We will quantitate the two binding mechanisms in a number of model cell systems, including the activated macrophage, the Kupffer cell and selected macrophage-like cell lines. We propose to demonstrate that type I leishmania binding is mediated by the macrophage CR3, that this binding triggers a respiratory burst, and restricts the intracellular growth of leishmania. We also propose to demonstrate that type II leishmania binding is mediated by the macrophage CR1, that binding to this receptor does not trigger the respiratory burst, and that this receptor is permissive for leishmania growth.
