Phagocyte activation is the first step in the process of phagocytosis. It involves activation of resting the phagocytes through inflammatory mediators such as bacterial products including bacterial proteins, capsules, LPS, peptidoglycan, and teichoic acids, complement proteins, inflammatory cytokines, and prostaglandins. The activated phagocytes are squeezed out of the capillaries and move towards the site of infection under the influence of chemoattractants by a process known as chemotaxis. Chemoattractants are mainly the chemicals released by microbes like bacteria or by injured/infected host cells. In addition, phagocytes also increase their ATP production, lethal oxidants, and lysosomal enzymes. Sometimes, the phagocytes can also encounter pathogens in the bloodstream without undergoing chemotaxis.
After reaching the site of infection, phagocytes bind to the pathogen or the infected cell to initiate the process of ingestion. The binding is accomplished with the help of different surface receptors present on phagocytes which can identify and bind to foreign pathogen/infected cell.
Ingestion and formation of phagolysosome
Phagocytes start ingesting the infected cell or pathogen once they bind to their target. The process of ingestion is initiated due to a series of signaling events that cause physical or chemical changes in the phagocytes. The phagocytes undergo membrane remodeling and develop structures called pseudopods that cover the pathogen, forming a cup shaped depression known as phagocytic cup at their point of contact. The plasma membrane of the phagocytes now surrounds the pathogen and within few minutes, the cup closes at its distal end, completely enclosing the pathogen. Later, it pinches off to form a new structure called phagosome. Phagosome is the vesicle/bubble like structure that encloses the pathogen.
Inside the cytoplasm of phagocytes, the phagosome now fuses with lysosome to form a structure called phagolysosome. The process of formation of phagolysosome is also known as phagosome maturation. Phagolysosome is a digestive vacuole that contains the digestive enzymes of lysosomes which are necessary for digesting and killing the pathogen.
Killing of pathogen
The killing and digestion of pathogen takes place inside the phagolysosome. Phagolysosome is the ultimate organelle that is responsible for destroying the pathogen. It has an acidic environment and number of digestive enzymes to kill the pathogen. These enzymes are capable of digesting proteins, nucleic acids (DNA/RNA), polysaccharides, and lipids (all macromolecules). The acidic environment neutralizes the pathogen and ensures that the pathogen cannot infect the phagolysosome. However, there are some pathogens like influenza viruses that can escape the phagolysosome by exploiting the lower pH environment. These viruses can escape into the cytoplasm where they can replicate. Phagocytes can destroy such viruses by engulfing the entire infected cell (that undergoes apoptosis in response to viral infection), as viruses cannot survive without the infected host cell. This prevents the spread of infection to the other cells. Thus, the phagolysosome can kill both the pathogen as well as the infected cell.
After killing the pathogen, phagolysosomes form residual bodies containing undigested materials which are removed outside the cell through exocytosis.
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