The key stages in phagocytosis and phagosome maturation. A microbe initially binds via molecules on its surface to receptors on the plasma membrane of the phagocyte. This activates the receptors, causing the initiation of intracellular signaling pathways, most prominently those leading to the membrane-dependent assembly of actin filaments and the exocytosis of various membrane compartments. These poorly understood processes in turn lead to the outgrowth of membrane-bounded projections, filopodia, that engulf the pathogen to form the phagosome, a cytoplasmic compartment containing the pathogen and bounded by a single membrane. Subsequent actin- and microtubule-dependent transport leads to the sequential fusion of the phagosome with other membrane-bounded compartments such as endosomes, vesicles of the trans Golgi network, and lysosomes. This phagosome maturation process results in alterations in the composition of phagosome contents and membrane as the phagosome acquires molecules delivered by fusion events and loses molecules by recycling of selected components via vesicular or tubular budding. The lower right-hand side of the diagram shows the 'normal' maturation pathway of a phagosome containing a non-pathogen, which is driven by fusion and recycling events involving the organelles listed. In this phagosome, the pathogen has been killed and digested by enzymes that are active at the low pH of the mature phagosome. The lower left-hand side of the diagram shows the maturation of a phagosome containing a persisting pathogen. The dotted line indicates that some of the compartments, most notably the late endosomes and lysosomes, fail to deliver their microbicidal contents into the phagosome, and the pathogen is not killed.