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Phagocytes attack foreign cells that they encounter but leave host cells alone. How is a phagocyte able to distinguish a foreign cell from a host cell? All cells have on their surface an array of proteins and other molecules, as we saw in Chapters 5 and 9. Phagocytes detect surface molecules that are common to pathogens, but not to the host.

Toll-like receptors (TLRs) are proteins on the surface of phagocytes that recognize and bind to molecules on pathogens. First discovered in the fruit fly Drosophila, TLRs are found on cells in vertebrates and invertebrates, and similar molecules are found in plants and bacteria, indicating that they are an early, evolutionarily conserved part of the innate immune system. They provide one of the earliest signals that an infection is present. TLRs recognize evolutionarily conserved surface molecules on a wide range of microorganisms. For example, one type of TLR recognizes a glycolipid on the cell wall of certain bacteria. Another recognizes a protein that is part of the bacterial flagellum.

Binding of TLRs to surface molecules on the pathogen is a signal to the phagocyte to engulf and destroy its target. Following binding of a foreign molecule to the TLR, phagocytes send a signal to the rest of the immune system that the body is under attack by releasing chemical messengers called cytokines that recruit other immune cells to the site of injury or infection. Cytokines, like hormones, provide long-distance communication between cells (Chapters 9 and 38).