Phagocytosis of microbes: complexity in action.
The phagocytic response of innate immune cells such as macrophages is defined by the activation of complex signaling networks that are stimulated by microbial contact. Many individual proteins have been demonstrated to participate in phagocytosis, and the application of high-throughput tools has indicated that many more remain to be described. In this review, we examine this complexity and describe how during recognition, multiple receptors are simultaneously engaged to mediate internalization, activate microbial killing, and induce the production of inflammatory cytokines and chemokines. Many signaling molecules perform multiple functions during phagocytosis, and these molecules are likely to be key regulators of the process. Indeed, pathogenic microorganisms target many of these molecules in their attempts to evade destruction.
Underhill
David M
DM
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103, USA. dunderhill@systemsbiology.org
Ozinsky
Adrian
A
D000818:Animals; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology; D008565:Membrane Proteins; D008829:Microbiology; D018448:Models, Immunological; D010586:Phagocytes / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D011951:Receptors, Complement / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism
D018925:Chemokines; D016207:Cytokines; D008565:Membrane Proteins; D011951:Receptors, Complement; D017452:Receptors, IgG; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013481:Superoxides