Amoudruz P, Holmlund U, Saghafian-Hedengren S, Nilsson C, Sverremark-Ekström E
Department of Immunology, Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Clin Exp Immunol. 2009 Mar;155(3):387-94. doi: 10.1111/j.1365-2249.2008.03792.x.
The relative composition of the two major monocytic subsets CD14(+)CD16(-) and CD14(+)CD16(+) is altered in some allergic diseases. These two subsets display different patterns of Toll-like receptor levels, which could have implications for activation of innate immunity leading to reduced immunoglobulin E-specific adaptive immune responses. This study aimed to investigate if allergic status at the age of 5 years is linked to differences in monocytic subset composition and their Toll-like receptor levels, and further, to determine if Toll-like receptor regulation and cytokine production upon microbial stimuli is influenced by the allergic phenotype. Peripheral blood mononuclear cells from 5-year-old allergic and non-allergic children were stimulated in vitro with lipopolysaccharide and peptidoglycan. Cells were analysed with flow cytometry for expression of CD14, Toll-like receptors 2 and 4 and p38-mitogen-activated protein kinase (MAPK). The release of cytokines and chemokines [tumour necrosis factor, interleukin (IL)-1 beta, IL-6, IL-8, IL-10, IL-12p70] into culture supernatants was measured with cytometric bead array. For unstimulated cells there were no differences in frequency of the monocytic subsets or their Toll-like receptor levels between allergic and non-allergic children. However, monocytes from allergic children had a significantly lower up-regulation of Toll-like receptor 2 upon peptidoglycan stimulation. Further, monocytes from allergic children had a higher spontaneous production of IL-6, but there were no differences between the two groups regarding p38-MAPK activity or cytokine and chemokine production upon stimulation. The allergic subjects in this study have a monocytic population that seems to display a hyporesponsive state as implicated by impaired regulation of Toll-like receptor 2 upon peptidoglycan stimulation.
在某些过敏性疾病中，两个主要单核细胞亚群CD14(+)CD16(-)和CD14(+)CD16(+)的相对组成会发生改变。这两个亚群表现出不同模式的Toll样受体水平，这可能对先天免疫激活产生影响，从而导致免疫球蛋白E特异性适应性免疫反应降低。本研究旨在调查5岁时的过敏状态是否与单核细胞亚群组成及其Toll样受体水平的差异有关，进而确定微生物刺激后Toll样受体调节和细胞因子产生是否受过敏表型的影响。来自5岁过敏和非过敏儿童的外周血单个核细胞在体外分别用脂多糖和肽聚糖刺激。通过流式细胞术分析细胞中CD14、Toll样受体2和4以及p38丝裂原活化蛋白激酶（MAPK）的表达。用细胞计数珠阵列检测培养上清液中细胞因子和趋化因子[肿瘤坏死因子、白细胞介素（IL）-1β、IL-6、IL-8、IL-10、IL-12p70]的释放。对于未刺激的细胞，过敏和非过敏儿童的单核细胞亚群频率或其Toll样受体水平没有差异。然而，肽聚糖刺激后，过敏儿童的单核细胞中Toll样受体2的上调明显较低。此外，过敏儿童的单核细胞自发产生IL-6的水平较高，但两组在刺激后的p38-MAPK活性或细胞因子和趋化因子产生方面没有差异。本研究中的过敏受试者的单核细胞群体似乎表现出一种低反应状态，肽聚糖刺激后Toll样受体2调节受损即表明了这一点。
