Altered innate immune response of plasmacytoid dendritic cells in multiple sclerosis

被引:26
作者
Bayas, A. [1 ]
Stasiolek, M. [3 ]
Kruse, N. [2 ]
Toyka, K. V. [1 ]
Selmaj, K. [3 ]
Gold, R. [2 ]
机构
[1] Univ Wurzburg, Dept Neurol, D-86156 Augsburg, Germany
[2] Univ & Gemeinnuetzige Hertie Stiftung, Fac Med, Inst MS Res, Gottingen, Germany
[3] Med Univ Lodz, Dept Neurol, Lodz, Poland
关键词
dendritic cell; innate; multiple sclerosis; plasmacytoid; Toll-like receptor; CENTRAL-NERVOUS-SYSTEM; TOLL-LIKE RECEPTORS; CPG OLIGODEOXYNUCLEOTIDES; MONONUCLEAR-CELLS; MESSENGER-RNA; CROSS-TALK; T-CELLS; ACTIVATION; EXPRESSION; CYTOKINES;
D O I
10.1111/j.1365-2249.2009.03964.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Plasmacytoid dendritic cells (pDCs) are of crucial importance in immune regulation and response to microbial factors. In multiple sclerosis ( MS), pDCs from peripheral blood showed an immature phenotype, but its role in susceptibility to MS is not determined. Because infectious diseases are established triggers of exacerbations in MS, in this study we have characterized the expression of Toll-like receptors (TLR) and the maturation and functional properties of peripheral blood pDCs from clinically stable, untreated MS patients in response to signals of innate immunity. After stimulation of TLR-9, interferon (IFN)-alpha production by pDCs was significantly lower in MS (n = 12) compared to healthy controls (n = 9). In an allogenic two-step co-culture assay we found an impaired effect of TLR-9 stimulation on IFN-gamma expression of autologous naive T cells in MS patients ( n = 4). In peripheral blood mononuclear cells, TLR-9 stimulation with type A CpG ODN resulted in a higher expression of TLR-1, -2, -4, -5 and -8 in MS patients (n = 7) compared with healthy controls (n = 11). These findings suggest an altered innate immune response to microbial stimuli in MS patients and may help understanding of why common infectious agents trigger MS attacks.
引用
收藏
页码:332 / 342
页数:11
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