Phagosome maturation proceeds independently of stimulation of toll-like receptors 2 and 4

Immunity. 2005 Oct;23(4):409-17. doi: 10.1016/j.immuni.2005.09.007.

Abstract

Toll-like receptors modulate many aspects of the innate immune response. Recent reports suggest that the maturation of phagosomes following particle uptake is modulated through signaling of Toll-like receptors. In the current study, the kinetics of phagosome maturation was evaluated quantitatively by ratio fluorometry to determine the lumenal pH of the phagosomes and a FRET-based technique to determine the degree of phagosome/lysosome fusion. Profiles generated for phagosomes containing experimental particles with or without the TLR ligands Pam3Cys-Ser-(Lys)4 or LPS failed to reveal a difference in maturation despite activating TLR-signaling pathways. Moreover, while macrophages defective in individual TLRs generated phagosome maturation profiles identical to wild-type macrophages, MyD88-deficient macrophages exhibited a marked depression in phagosome/lysosome fusion that appears independent of short-term TLR-mediated effects. The results demonstrate that the rate of maturation of phagosomes proceeds independently of TLR signaling pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Antigens, Differentiation / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Immunoglobulin G / immunology
  • Kinetics
  • Ligands
  • Lysosomes / metabolism
  • Mannose / immunology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Microspheres
  • Myeloid Differentiation Factor 88
  • Phagocytosis / immunology
  • Phagosomes / immunology*
  • Phagosomes / metabolism
  • Phosphatidylserines / immunology
  • Phosphatidylserines / pharmacology
  • Receptors, Immunologic / metabolism
  • Signal Transduction
  • Staphylococcus aureus / immunology
  • Time Factors
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 4 / immunology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Immunoglobulin G
  • Ligands
  • MYD88 protein, human
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Phosphatidylserines
  • Receptors, Immunologic
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Mannose