Yates Robin M, Russell David G
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Immunity. 2005 Oct;23(4):409-17. doi: 10.1016/j.immuni.2005.09.007.
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.
Toll样受体调节先天性免疫反应的许多方面。最近的报道表明，颗粒摄取后吞噬体的成熟是通过Toll样受体的信号传导来调节的。在本研究中，通过比率荧光法定量评估吞噬体成熟的动力学，以确定吞噬体的腔pH值，并使用基于荧光共振能量转移（FRET）的技术来确定吞噬体/溶酶体融合的程度。尽管激活了TLR信号通路，但含有或不含有TLR配体Pam3Cys-Ser-(Lys)4或LPS的实验颗粒的吞噬体所产生的图谱未能显示出成熟方面的差异。此外，虽然单个TLR缺陷的巨噬细胞产生的吞噬体成熟图谱与野生型巨噬细胞相同，但MyD88缺陷的巨噬细胞在吞噬体/溶酶体融合方面表现出明显的抑制，这似乎与短期TLR介导的效应无关。结果表明，吞噬体的成熟速率独立于TLR信号通路进行。
