Scott Karen, Manunta Maria, Germain Conrad, Smith Peter, Jones Meleri, Mitchell Peter, Dessi Daniele, Branigan Bamford Kathleen, Lechler Robert I, Fiori Pier Luigi, Foster Graham R, Lombardi Giovanna
Department of Immunology, Division of Medicine, Faculty of Medicine, Imperial College at Hammersmith Hospital, London, United Kingdom.
Immunology. 2005 Oct;116(2):245-54. doi: 10.1111/j.1365-2567.2005.02218.x.
Dendritic cells produce cytokines that regulate the class of the adaptive immune response. Microbial recognition is mediated, at least in part, by pattern recognition receptors such as Toll-like receptors, which influence dendritic cell maturation. In humans it is not yet clear how intact pathogens modulate the developing immune response. To address the effects of intact pathogens on the maturation and effector functions of human dendritic cells, we investigated their responses to a number of microbial pathogens. We studied a range of micro-organisms including Gram-negative bacteria (Escherichia coli and Salmonella enterica sv. typhimurium), Gram-positive cocci (Staphylococcus aureus) and atypical bacteria (Mycobacterium tuberculosis and Mycoplasma hominis) as well as the human protozoal parasite Trichomonas vaginalis. The micro-organisms were fixed in formaldehyde to prevent replication whilst preserving surface morphology. All the pathogens induced similar up-regulation of dendritic cell activation-associated cell surface markers but there was a profound difference in the patterns of cytokines produced by the stimulated dendritic cells. Some pathogens (E. coli, Salmonella enterica sv. typhimurium and S. aureus) induced interleukin-12 (IL-12), IL-10 and interferon-alpha whereas others (M. tuberculosis, Mycoplasma hominis and T. vaginalis) induced only IL-10. This differential effect was not altered by costimulation of the dendritic cells through CD40. These results support the notion that human dendritic cells are plastic in their response to microbial stimuli and that the nature of the pathogen dictates the response of the dendritic cell.
树突状细胞产生调节适应性免疫反应类型的细胞因子。微生物识别至少部分是由模式识别受体介导的，如Toll样受体，其影响树突状细胞的成熟。在人类中，完整病原体如何调节发育中的免疫反应尚不清楚。为了研究完整病原体对人树突状细胞成熟和效应功能的影响，我们研究了它们对多种微生物病原体的反应。我们研究了一系列微生物，包括革兰氏阴性菌（大肠杆菌和鼠伤寒沙门氏菌）、革兰氏阳性球菌（金黄色葡萄球菌）和非典型细菌（结核分枝杆菌和人型支原体）以及人类原生动物寄生虫阴道毛滴虫。将微生物用甲醛固定以防止其复制，同时保留表面形态。所有病原体均诱导树突状细胞活化相关细胞表面标志物出现相似的上调，但刺激后的树突状细胞产生的细胞因子模式存在显著差异。一些病原体（大肠杆菌、鼠伤寒沙门氏菌和金黄色葡萄球菌）诱导产生白细胞介素-12（IL-12）、IL-10和α干扰素，而其他病原体（结核分枝杆菌、人型支原体和阴道毛滴虫）仅诱导产生IL-10。通过CD40对树突状细胞进行共刺激并不会改变这种差异效应。这些结果支持这样一种观点，即人树突状细胞对微生物刺激的反应具有可塑性，病原体的性质决定了树突状细胞的反应。
