Blander J Magarian, Medzhitov Ruslan
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Science. 2004 May 14;304(5673):1014-8. doi: 10.1126/science.1096158.
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.
在高等后生动物中,吞噬作用对于宿主抵御微生物病原体以及清除凋亡细胞至关重要。微生物细胞和凋亡细胞都通过从吞噬体到溶酶体的共同途径进行传递以便降解。在此,我们发现细菌激活Toll样受体(TLR)信号通路,而非凋亡细胞,在包括内化和吞噬体成熟在内的多个步骤调节吞噬作用。在缺乏TLR信号时,细菌的吞噬作用受损。观察到两种吞噬体成熟模式,即组成型和诱导型;它们的差异参与取决于货物触发TLR信号的能力。