syphilis—hides from phagocytes by coating its surface with fibronectin, which is produced naturally by the body and plays a crucial role in wound healing. avoiding engulfment bacteria often produce capsules made of proteins or sugars that coat their cells and interfere with phagocytosis. some examples are the k5 capsule and o75 o antigen found on the surface of escherichia coli, and the exopolysaccharide capsules of staphylococcus epidermidis. streptococcus pneumoniae produces several types of capsule that provide different levels of protection, and group a streptococci produce proteins such as m protein and fimbrial proteins to block engulfment. some proteins hinder opsonin-related ingestion; staphylococcus aureus produces protein a to block antibody receptors, which decreases the effectiveness of opsonins. enteropathogenic species of the genus yersinia bind with the use of the virulence factor yoph to receptors of phagocytes from which they influence the cells capability to exert phagocytosis. survival inside the phagocyte rickettsia are small bacteria—here stained red—that grow in the cytoplasm of non-professional phagocytes. bacteria have developed ways to survive inside phagocytes, where they continue to evade the immune system. to get safely inside the phagocyte they express proteins called invasins. when inside the cell they remain in the cytoplasm and avoid toxic chemicals contained in the phagolysosomes. some bacteria prevent the fusion of a phagosome and lysosome, to form the phagolysosome. other pathogens, such as leishmania, create a highly modified vacuole inside the phagocyte, which helps them persist and replicate. some bacteria are capable of living inside of the phagolysosome. staphylococcus aureus, for example, produces the enzymes catalase and superoxide dismutase, which break down chemicals—such as hydrogen peroxide—produced by phagocytes to kill bacteria. bacteria may escape from the phagosome before the formation of the phagolysosome: listeria monocytogenes can make a hole in the phagosome wall using enzymes called listeriolysin o and phospholipase c. killing bacteria have developed several ways of killing phagocytes. these include cytolysins, which form pores in the phagocyte's cell membranes, streptolysins and leukocidins, which cause neutrophils' granules to rupture and release toxic substances, and exotoxins that reduce the supply of a phagocyte's atp, needed for phagocytosis. after a bacterium is ingested, it may kill the phagocyte by releasing toxins that travel through the phagosome or phagolysosome membrane to target other parts of the cell. disruption of cell signaling leishmania tropica amastigotes (arrows) in a macrophage from skin some survival strategies often involve disrupting cytokines and other methods of cell signaling to prevent the phagocyte's responding to invasion. the protozoan parasites toxoplasma gondii, trypanosoma cruzi, and leishmania infect macrophages, and each has a unique way of taming them. some species of leishmania alter the infected macrophage's signalling, repress the production of cytokines and microbicidal molecules—nitric oxide and reactive oxygen species—and compromise antigen presentation. host damage by phagocytes macrophages and neutrophils, in particular, play a central role in the inflammatory process by releasing proteins and small-molecule inflammatory mediators that control infection but can damage host tissue. in general, phagocytes aim to destroy pathogens by engulfing them and subjecting them to a battery of toxic chemicals inside a phagolysosome. if a phagocyte fails to engulf its target, these toxic agents can be released into the environment (an action referred to as "frustrated phagocytosis"). as these agents are also toxic to host cells, they can cause extensive damage to healthy cells and tissues. when neutrophils release their granule contents in the kidney, the contents of the granule (reactive oxygen compounds and proteases) degrade the extracellular matrix of host cells and can cause damage to glomerular cells, affecting their ability to filter blood and causing changes in shape. in addition, phospholipase products (e.g., leukotrienes) intensify the damage. this release of substances promotes chemotaxis of more neutrophils to the site of infection, and glomerular cells can be damaged further by the adhesion molecules during the migration of neutrophils. the injury done to the glomerular cells can cause kidney failure. neutrophils also play a key role in the development of most forms of acute lung injury. here, activated neutrophils release the contents of their toxic granules into the lung environment. experiments have shown that a reduction in the number of neutrophils lessens the effects of acute lung injury, but treatment by inhibiting neutrophils is not clinically realistic, as it would leave the host vulnerable to infection. in the liver, damage by neutrophils can contribute to dysfunction and injury in response to the release of endotoxins produced by bacteria, sepsis, trauma, alcoholic hepatitis, ischemia, and hypovolemic shock resulting from acute hemorrhage. chemicals released by macrophages can also damage host tissue. tnf-α is an important chemical that is released by macrophages that causes the blood in small vessels to clot to prevent an infection from spreading. if a bacterial infection spreads to the blood, tnf-α is released into vital organs, which can cause vasodilation and a decrease in plasma volume; these in turn can be followed by septic shock. during septic shock, tnf-α release causes a blockage of the small vessels that supply blood to the vital organs, and the organs may fail. septic shock can lead to death. evolutionary origins false-color scanning electron microscope image of streptococcus pyogenes (orange) during phagocytosis with a human neutrophil (blue) phagocytosis is common and probably appeared early in evolution, evolving first in unicellular eukaryotes. amoebae are unicellular protists that separated from the tree leading to metazoa shortly after the divergence of plants, and they share many specific functions with mammalian phagocytic cells. dictyostelium discoideum, for example, is an amoeba that lives in the soil and feeds on bacteria. like animal phagocytes, it engulfs bacteria by phagocytosis mainly through toll-like receptors, and it has other biological functions in common with macrophages. dictyostelium discoideum is social; it aggregates when starved to form a migrating pseudoplasmodium or slug. this multicellular organism eventually will produce a fruiting body with spores that are resistant to environmental dangers. before the formation of fruiting bodies, the cells will migrate as a slug-like organism for several days. during this time, exposure to toxins or bacterial pathogens has the potential to compromise survival of the species by limiting spore production. some of the amoebae engulf bacteria and absorb toxins while circulating within the slug, and these amoebae eventually die. they are genetically identical to the other amoebae in the slug; their self-sacrifice to protect the other amoebae from bacteria is similar to the self-sacrifice of phagocytes seen in the immune system of higher vertebrates. this ancient immune function in social amoebae suggests an evolutionarily conserved cellular foraging mechanism that might have been adapted to defense functions well before the diversification of amoebae into higher forms. phagocytes occur throughout the animal kingdom, from marine sponges to insects and lower and higher vertebrates. the ability of amoebae to distinguish between self and non-self is a pivotal one, and is the root of the immune system of many species of amoeba.