Regulation of phagosome maturation by signals from toll-like receptors.
In higher metazoans, phagocytosis is essential in host defense against microbial pathogens and in clearance of apoptotic cells. Both microbial and apoptotic cells are delivered on a common route from phagosomes to lysosomes for degradation. Here, we found that activation of the Toll-like receptor (TLR) signaling pathway by bacteria, but not apoptotic cells, regulated phagocytosis at multiple steps including internalization and phagosome maturation. Phagocytosis of bacteria was impaired in the absence of TLR signaling. Two modes of phagosome maturation were observed, constitutive and inducible; their differential engagement depended on the ability of the cargo to trigger TLR signaling.
Blander
J Magarian
JM
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Medzhitov
Ruslan
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D017209:Apoptosis; D001419:Bacteria / Q000276:immunology* / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004926:Escherichia coli / Q000276:immunology / Q000502:physiology; D008247:Lysosomes / Q000648:ultrastructure; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016253:Microscopy, Immunoelectron; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88; D010587:Phagocytosis; D010588:Phagosomes / Q000382:microbiology / Q000502:physiology* / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology / Q000502:physiology; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology / Q000502:physiology; D051193:Toll-Like Receptors; D048051:p38 Mitogen-Activated Protein Kinases
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D004791:Enzyme Inhibitors; D008562:Membrane Glycoproteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D051193:Toll-Like Receptors; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases