Regulation of phagosome maturation by signals from toll-like receptors

Science. 2004 May 14;304(5673):1014-8. doi: 10.1126/science.1096158.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Antigens, Differentiation / metabolism
  • Apoptosis
  • Bacteria / immunology*
  • Bacteria / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Escherichia coli / immunology
  • Escherichia coli / physiology
  • Lysosomes / ultrastructure
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Macrophages / ultrastructure
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Microscopy, Immunoelectron
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Myeloid Differentiation Factor 88
  • Phagocytosis*
  • Phagosomes / microbiology
  • Phagosomes / physiology*
  • Phagosomes / ultrastructure
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Immunologic / metabolism
  • Recombinant Proteins / metabolism
  • Salmonella typhimurium / immunology
  • Salmonella typhimurium / physiology
  • Signal Transduction*
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / physiology
  • Toll-Like Receptors
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Enzyme Inhibitors
  • Membrane Glycoproteins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Recombinant Proteins
  • Toll-Like Receptors
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases