Peduzzi Elisabetta, Groeper Célia, Schütte Daniela, Zajac Paul, Rondini Simona, Mensah-Quainoo Ernestina, Spagnoli Giulio Cesare, Pluschke Gerd, Daubenberger Claudia Andrea
Swiss Tropical Institute, Department of Medical Parasitology and Molecular Immunology, Basel, Switzerland.
J Invest Dermatol. 2007 Mar;127(3):638-45. doi: 10.1038/sj.jid.5700593. Epub 2006 Oct 19.
Buruli ulcer (BU) caused by Mycobacterium ulcerans is a chronic necrotizing disease of the skin and the underlying soft tissue. Fat tissue necrosis accompanied by minimal inflammation is considered the most reliable histopathologic feature of BU. There may be a constant influx of inflammatory cells to the sites of active infection but these are thought to be killed by mycolactone, a polyketide toxin produced by M. ulcerans, through apoptosis and necrosis. Here we describe the spatial correlations between mycobacterial load and the expression of dendritic cell (DC) surface markers (cluster of differentiation (CD)83, CD11c, and CD123), the Toll-like receptor (TLR) 9 and pro- and anti-inflammatory cytokines (IL-8, IL-6, tumor necrosis factor-alpha (TNF-alpha), IFN-alpha, IL-12p40, IL-10, and IFN-gamma) within BU lesions. Although IL-8, IL-6, and TNF-alpha messenger RNA (mRNA) was detectable by real-time PCR in all lesions, the expression of the other cytokines was only found as small foci in some lesions. Correlations of the distribution of mRNA encoding the activation marker CD83 and the DC subset markers CD123 and CD11c indicate that both activated plasmacytoid and myeloid dendritic cells were present in the lesions. Results suggest that M. ulcerans specific immune responses may develop once therapeutic interventions have limited the production of mycolactone.
由溃疡分枝杆菌引起的布鲁里溃疡（BU）是一种皮肤及皮下软组织的慢性坏死性疾病。脂肪组织坏死伴轻微炎症被认为是布鲁里溃疡最可靠的组织病理学特征。在活跃感染部位可能不断有炎性细胞涌入，但这些细胞被认为会被溃疡分枝杆菌产生的聚酮毒素——分枝杆菌内酯通过凋亡和坏死作用杀死。在此，我们描述了布鲁里溃疡病灶内分枝杆菌载量与树突状细胞（DC）表面标志物（分化簇（CD）83、CD11c和CD123）、Toll样受体（TLR）9以及促炎和抗炎细胞因子（IL-8、IL-6、肿瘤坏死因子-α（TNF-α）、IFN-α、IL-12p40、IL-10和IFN-γ）表达之间的空间相关性。尽管通过实时PCR在所有病灶中均可检测到IL-8、IL-6和TNF-α信使核糖核酸（mRNA），但其他细胞因子的表达仅在部分病灶中呈小灶状发现。编码活化标志物CD83以及DC亚群标志物CD123和CD11c的mRNA分布相关性表明，病灶中同时存在活化的浆细胞样树突状细胞和髓样树突状细胞。结果提示，一旦治疗干预限制了分枝杆菌内酯的产生，可能会引发针对溃疡分枝杆菌的特异性免疫反应。
