Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers and Function in Filarial Infection
Human Monocyte Subsets at Homeostasis and Their Perturbation in Numbers and Function in Filarial Infection
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DOI：
10.1128/iai.01973-14
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发表时间：
2014-11-01
影响因子：
3.1
通讯作者：
Nutman, Thomas B.
中科院分区：
文献类型：
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作者：
Semnani, Roshanak Tolouei;Moore, Vanessa;Nutman, Thomas B.
为了表征人类主要循环单核细胞群的功能和可塑性，并探讨它们在系统性蠕虫感染中的作用，我们在稳态和激活后检测了高度纯化（通过基于流的分选）的人类单核细胞亚群(CD14(hi)/CD16（阴性）[经典]、CD14（+或hi)/CD16（中等）[中间]和CD14（阴性）/CD16(hi)[非经典]）。在这三个亚群中，经典亚群和中间亚群被发现是炎症和调节细胞因子的主要来源，以及与替代激活相关的细胞因子/趋化因子，而非经典和经典人群则表现出通过内皮单层转移的能力。此外，主要是经典亚群在促进自体T细胞增殖方面最有效。这些亚群的分布在系统性蠕虫（班氏乌氏杆菌）感染的情况下发生了变化，使得非经典单核细胞在丝虫病感染中扩增（几乎翻了两倍），从而改变了这些单核细胞亚群的频率和分布。为了进一步了解丝虫/单核细胞界面，体外模型表明，经典亚群比其他两个亚群更有效地内化丝虫抗原，但寄生虫驱动的调节性细胞因子白细胞介素-10仅来自中间亚群。我们的数据表明，单核细胞亚群在体内平衡和对寄生虫的反应中具有不同的功能。
To characterize the function and plasticity of the major human circulating monocyte populations and to explore their role in systemic helminth infection, highly purified (by flow-based sorting) human monocyte subsets (CD14(hi)/CD16(neg) [classical], CD14(+ or hi)/CD16(med) [intermediate], and CD14(neg)/CD16(hi) [nonclassical]) were examined at homeostasis and after activation. Among these three subsets the classical and intermediate subsets were found to be the major sources of inflammatory and regulatory cytokines, as well as cytokines/chemokines associated with alternative activation, whereas the nonclassical and classical populations demonstrated an ability to transmigrate through endothelial monolayers. Moreover, it was primarily the classical subset that was the most efficient in promoting autologous T cell proliferation. The distribution of these subsets changed in the context of a systemic helminth (Wuchereria bancrofti) infection such that patent infection altered the frequency and distribution of these monocyte subsets with the nonclassical monocytes being expanded (almost 2-fold) in filarial infection. To understand further the filarial/monocyte interface, in vitro modeling demonstrated that the classical subset internalized filarial antigens more efficiently than the other two subsets but that the parasite-driven regulatory cytokine interleukin-10 was exclusively coming from the intermediate subset. Our data suggest that monocyte subsets have a differential function at homeostasis and in response to helminth parasites.