An overview of phagocytic and non-phagocytic pathways. A) Phagocytosis occurs in macrophages through an actin-based mechanism involving interaction with various specialized cell surface receptors (e.g., mannose, IgG, complement, Fcγ receptors). The foreign particles recognized by specific receptors, often targeting surface-bound opsonins, are internalized to form endocytic vesicles called phagosomes. The fusion of phagosomes with the lysosomal compartment leads to the formation of phagolysosomes, where the foreign particles are enzymatically degraded. B) Clathrin-mediated endocytosis involves the formation of vesicles from triskelion clathrin-coated regions of the plasma membrane. The triskelion clathrin in the cytosol are then recycled back to the plasma membrane followed by movement of ingested materials from early endosome to the late endosome, finally fusing with lysosome to form the lysosome-endosome hybrid. The materials are then degraded by the low pH and enzyme-rich environment of the endo-lysosomal vesicle. C) Caveolin-mediated endocytosis involves internalization through caveolin (a dimeric protein) enriched invaginations. The cytosolic caveolin vesicle then delivers its contents to endosomes, to form caveosomes which can avoid lysosomal enzymatic degradation, and are transported along the cytoskeleton to the endoplasmic reticulum/golgi complex. D) Macropinocytosis is a clathrin- and caveolin-independent pathway. It involves the formation of large vesicles called macropinosomes, which occurs through actin filament driven plasma membrane protrusions. The contents are degraded following fusion with the lysosomal compartment. (Figure partially adapted from Hillaireau and Couvreur, Cell. Mol. Life Sci. 2009, 66, 2873–2896).