Phagosome

In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials (e.g. amino acids) from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens. In cell biology, a phagosome is a vesicle formed around a particle engulfed by a phagocyte via phagocytosis. Professional phagocytes include macrophages, neutrophils, and dendritic cells (DCs). A phagosome is formed by the fusion of the cell membrane around a microorganism, a senescent cell or an apoptotic cell. Phagosomes have membrane-bound proteins to recruit and fuse with lysosomes to form mature phagolysosomes. The lysosomes contain hydrolytic enzymes and reactive oxygen species (ROS) which kill and digest the pathogens. Phagosomes can also form in non-professional phagocytes, but they can only engulf a smaller range of particles, and do not contain ROS. The useful materials (e.g. amino acids) from the digested particles are moved into the cytosol, and waste is removed by exocytosis. Phagosome formation is crucial for tissue homeostasis and both innate and adaptive host defense against pathogens. However, some bacteria can exploit phagocytosis as an invasion strategy. They either reproduce inside of the phagolysosome (e.g. Coxiella spp.) or escape into the cytoplasm before the phagosome fuses with the lysosome (e.g. Rickettsia spp.).Many Mycobacteria, including Mycobacterium tuberculosisand Mycobacterium avium paratuberculosis, can manipulate the host macrophage to prevent lysosomes from fusing with phagosomes and creating mature phagolysosomes. Such incomplete maturation of the phagosome maintains an environment favorable to the pathogens inside it. Phagosomes are large enough to degrade whole bacteria, or apoptotic and senescent cells, which are usually >0.5μm in diameter. This means a phagosome is several orders of magnitude bigger than an endosome, which is measured in nanometres. Phagosomes are formed when pathogens or opsonins bind to a transmembrane receptor, which are randomly distributed on the phagocyte cell surface. Upon binding, 'outside-in' signalling triggers actin polymerisation and pseudopodia formation, which surrounds and fuses behind the microorganism. Protein kinase C, phosphoinositide 3-kinase, and phospholipase C (PLC) are all needed for signalling and controlling particle internalisation. More cell surface receptors can bind to the particle in a zipper-like mechanism as the pathogen is surrounded, increasing the binding avidity. Fc receptor (FcR), complement receptors (CR), mannose receptor and Dectin-1 are phagocytic receptors, which means that they can induce phagocytosis if they are expressed in non-phagocytic cells such as fibroblasts. Other proteins such as Toll-like receptors are involved in pathogen pattern recognition and are often recruited to phagosomes but do not specifically trigger phagocytosis in non-phagocytic cells, so they are not considered phagocytic receptors. Opsonins are molecular tags such as antibodies and complements that attach to pathogens and up-regulate phagocytosis. Immunoglobulin G (IgG) is the major type of antibody present in the serum. It is part of the adaptive immune system, but it links to the innate response by recruiting macrophages to phagocytose pathogens. The antibody binds to microbes with the variable Fab domain, and the Fc domain binds to Fc receptors (FcR) to induce phagocytosis. Complement-mediated internalisation has much less significant membrane protrusions, but the downstream signalling of both pathways converge to activate Rho GTPases. They control actin polymerisation which is required for the phagosome to fuse with endosomes and lysosomes. Other non-professional phagocytes have some degree of phagocytic activity, such as thyroid and bladder epithelial cells that can engulf erythrocytes and retinal epithelial cells that internalise retinal rods. However non-professional phagocytes do not express specific phagocytic receptors such as FcR and have a much lower rate of internalisation. Some invasive bacteria can also induce phagocytosis in non-phagocytic cells to mediate host uptake. For example, Shigella can secrete toxins that alter the host cytoskeleton and enter the basolateral side of enterocytes. As the membrane of the phagosome is formed by the fusion of the plasma membrane, the basic composition of the phospholipid bilayer is the same. Endosomes and lysosomes then fuse with the phagosome to contribute to the membrane, especially when the engulfed particle is very big, such as a parasite. They also deliver various membrane proteins to the phagosome and modify the organelle structure.