Macrophages are key regulators of the innate immune response, as front line responders to infection and pathogen invasion. These cells typically ingest and kill bacteria but they can also be colonized by opportunistic bacteria. The macrophage plasma membrane is the environment responsible for undertaking surveillance, and for internalization of pathogens. The cell surface is highly dynamic with structures such as filopodia and dorsal ruffles that give rise to macropinosomes and phagosomes.
Rab GTPase proteins regulate membrane ruffling, and the formation of phagosomes and members of this family are often targeted by bacterial effectors.
A cascade of Rab proteins is recruited to sites of pathogen contact and phagocytosis. Here we focus on three Rabs 13, 34, 35 that are recruited to plasma membrane ruffles via a polybasic tail domain. Overexpression of dominant-negative & constitutively-active Rab mutants, and siRNA knockdowns were utilized to demonstrate the novel roles for each Rab in Fcγ phagocytosis and in the entry of Salmonella typhimurium. We identify an early stage Rab regulatory unit that is critical for pathogen entry and uptake.