Divergence of macrophage phagocytic and antimicrobial programs in leprosy.
Divergence of macrophage phagocytic and antimicrobial programs in leprosy.
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DOI：
10.1016/j.chom.2009.09.002
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发表时间：
2009-10-22
影响因子：
30.3
通讯作者：
Modlin RL
中科院分区：
文献类型：
--
作者：
Montoya D;Cruz D;Teles RM;Lee DJ;Ochoa MT;Krutzik SR;Chun R;Schenk M;Zhang X;Ferguson BG;Burdick AE;Sarno EN;Rea TH;Hewison M;Adams JS;Cheng G;Modlin RL
针对许多微生物病原体的有效先天免疫需要巨噬细胞程序上调吞噬作用和直接抗菌途径，这两种功能通常被认为是协同调节的。在这里，这些关键功能的调节在人血液来源的巨噬细胞中进行了研究。IL-10诱导吞噬途径，包括CD 209和清道夫受体，导致分枝杆菌和oxLDL的吞噬作用。IL-15诱导维生素D依赖性抗微生物途径和CD 209，但细胞的吞噬作用较弱。通过对麻风病病变谱的分析，证实了巨噬细胞功能程序的差异调节：巨噬细胞吞噬途径在临床进行性多杆菌形式中是突出的，而维生素D依赖性抗菌途径在疾病的自限性形式和经历从多杆菌到自限性形式的逆转反应的患者中占主导地位。这些数据表明，巨噬细胞的吞噬作用和抗菌反应的程序是不同的和差异调节的先天免疫细菌感染。
Effective innate immunity against many microbial pathogens requires macrophage programs that upregulate phagocytosis and direct antimicrobial pathways, two functions generally assumed to be coordinately regulated. Here the regulation of these key functions was investigated in human blood-derived macrophages. IL-10 induced the phagocytic pathway, including CD209 and scavenger receptors, resulting in phagocytosis of mycobacteria and oxLDL. IL-15 induced the vitamin D-dependent antimicrobial pathway and CD209, yet the cells were less phagocytic. The differential regulation of macrophage functional programs was confirmed by analysis of the spectrum of leprosy lesions: the macrophage phagocytosis pathway was prominent in the clinically progressive, multibacillary form, whereas the vitamin D-dependent antimicrobial pathway predominated in the self-limited form of the disease and in patients undergoing reversal reactions from the multibacillary to the self-limited form. These data indicate that macrophage programs for phagocytosis and antimicrobial responses are distinct and differentially regulated in innate immunity in bacterial infections.
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