Alternatively Activated and Immunoregulatory Monocytes in Human Filarial Infections
Alternatively Activated and Immunoregulatory Monocytes in Human Filarial Infections
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DOI：
10.1086/599090
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发表时间：
2009-06-15
影响因子：
6.4
通讯作者：
Nutman, Thomas B.
中科院分区：
文献类型：
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作者：
Babu, Subash;Kumaraswami, V.;Nutman, Thomas B.
背景资料。丝虫感染动物的单核细胞/巨噬细胞表现出交替激活的表型；然而，在人类丝虫感染中，单核细胞的交替激活表型知之甚少。为了阐明丝虫感染中单核细胞的活化和细胞因子谱，我们检测了无症状丝虫感染者和非丝虫感染者外周血单核细胞中精氨酸酶、一氧化氮合酶2、选择性激活标志物和细胞因子基因的表达模式，以及丝虫抗原(丝虫抗原[BMA])的反应。无症状丝虫感染患者单核细胞NOS2表达显著降低，ARG1表达显著增强。这些变化与抵抗素、甘露糖受体C型(MRC1)、巨噬细胞C型半乳糖凝集素(MGL)和趋化因子配体18(CCL18)基因的表达显著增加有关。作为对BMA的反应，来自感染者的纯化单核细胞也表达显著较低水平的IL-12和IL-18，但相反，表达显著较高水平的转化生长因子β、IL-10和细胞因子信号转导抑制因子1mRNA。抑制精氨酸酶-1可显著降低抵抗素、MRC1、MGL和CCL18基因的表达，显著增强NOS2和IL-12、IL-18基因的表达。人类丝虫感染与单核细胞的存在有关，单核细胞具有交替激活的免疫调节表型。
Background. Monocytes/macrophages from filaria-infected animals exhibit an alternatively activated phenotype; however, very little is known about the alternative activation phenotype of monocytes in human filarial infection.Methods. To elucidate the activation and cytokine profile of monocytes in human filarial infection, we examined the expression patterns of genes encoding arginase, nitric oxide synthase 2, alternative activation markers, and cytokines in monocytes from individuals with asymptomatic filarial infection and individuals without filarial infection, ex vivo and in response to filarial antigen (Brugia malayi antigen [BmA]).Results. Monocytes from patients with asymptomatic filarial infection exhibited significantly diminished expression of NOS2 and significantly enhanced expression of ARG1. These changes were associated with significantly increased expression of the genes encoding resistin, mannose receptor C type 1 (MRC1), macrophage galactose type C lectin (MGL), and chemokine ligand 18 (CCL18). In response to BmA, purified monocytes from infected individuals also expressed significantly lower levels of interleukin (IL)-12 and IL-18 but, in contrast, expressed significantly higher levels of transforming growth factor beta, IL-10, and suppressor of cytokine signaling 1 mRNA. Inhibition of arginase-1 resulted in significantly diminished expression of the genes encoding resistin, MRC1, MGL, and CCL18, as well as significantly enhanced expression of NOS2 and the genes encoding IL-12 and IL-18.Conclusion. Patent human filarial infection is associated with the presence of monocytes characterized by an alternatively activated immunoregulatory phenotype.