Phagosome maturation proceeds independently of stimulation of toll-like receptors 2 and 4.
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.
Yates
Robin M
RM
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Russell
David G
DG
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007074:Immunoglobulin G / Q000276:immunology; D007700:Kinetics; D008024:Ligands; D008247:Lysosomes / Q000378:metabolism; D008358:Mannose / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008863:Microspheres; D053594:Myeloid Differentiation Factor 88; D010587:Phagocytosis / Q000276:immunology; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D010718:Phosphatidylserines / Q000276:immunology / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000378:metabolism; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D007074:Immunoglobulin G; D008024:Ligands; C507779:MYD88 protein, human; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D008358:Mannose