Phagocytosis and the inflammatory response.
Macrophages are a cornerstone of the innate immune system. They detect infectious organisms via a plethora of receptors, phagocytose them, and orchestrate an appropriate host response. Phagocytosis is extraordinarily complex: numerous receptors stimulate particle internalization, the cytoskeletal elements mediating internalization differ by receptor system and the nature of the pathogen being internalized, and the outcome can differ by bacterium. After generating a panel of 150 monoclonal antibodies that recognizes proteins recruited to the phagosome, analysis of novel phagocytic proteins was prioritized by focusing on those that behave differently during the internalization of virulent and avirulent bacteria. Several novel proteins that have roles in membrane extension were characterized. Although the inflammatory pathways leading to appropriate host response are reasonably well defined, it is not clear how macrophages define the threat precisely. Recent work indicates that Toll-like receptors play a key role in reading a "bar code" on invading microorganisms and in eliciting a specific immune response. The mechanisms and coupling to the phagocytic response are discussed.
Aderem
Alan
A
Institute for Systems Biology, Seattle, Washington 98103, USA. aderem@systemsbiology.org
D000818:Animals; D001419:Bacteria / Q000276:immunology; D001424:Bacterial Infections / Q000276:immunology; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D008562:Membrane Glycoproteins; D010587:Phagocytosis; D011956:Receptors, Cell Surface; D015398:Signal Transduction; D051193:Toll-Like Receptors; D014777:Virus Diseases / Q000276:immunology
D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors