Institute for Molecular Bioscience, University of Queensland, Brisbane 4072, Australia.
Macrophages are sentinels and front-line innate immune cells, charged with detecting and destroying pathogens. Accordingly, the macrophage cell surface is highly dynamic in order to accommodate cell migration, environmental sampling, protein secretion and receptor activation. Gram negative bacterial lipopolyscaccharide (LPS) activates macrophages through Toll-like receptor 4 (TLR4) – complexes within special domains on the cell surface. We have used a suite of GFP-Rab GTPases to define membrane domains at and near the macrophage cell surface that are shaped by exo- and endocytosis and which function to support TLR4 signaling. Specific domains defined by Rabs 5, 8, 35 and 31 are compared and contrasted by live cell imaging. Specific effectors for each of these Rabs have been defined and their roles in pathogen-induced phagocytosis and TLR4 signaling have been explored by siRNA or genetic inactivation. Our results show a highly dynamic series of Rab-defined membrane domains that acutely control innate inflammatory responses.