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首页> 外文期刊>Clinical and diagnostic laboratory immunology >Lipoprotein-Dependent and -Independent Immune Responses to Spirochetal Infection
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Lipoprotein-Dependent and -Independent Immune Responses to Spirochetal Infection

机译：脂蛋白依赖性和非依赖性对螺旋体感染的免疫反应。

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In this study, we used the epidermal suction blister technique, in conjunction with multiparameter flow cytometry, to analyze the cellular and cytokine responses elicited by intradermal injection of human volunteers with synthetic analogs for spirochetal lipoproteins and compared the responses to findings previously reported from patients with erythema migrans (EM). Compared with peripheral blood (PB), lipopeptides derived from the N termini of the Borrelia burgdorferi outer surface protein C and the 17-kDa lipoprotein of Treponema pallidum (OspC-L and 17-L, respectively) elicited infiltrates enriched in monocytes/macrophages and dendritic cells (DCs) but also containing substantial percentages of neutrophils and T cells. Monocytoid (CD11c+) and plasmacytoid (CD11c?) DCs were selectively recruited to the skin in ratios similar to those in PB, but only the former expressed the activation/maturation surface markers CD80, CD83, and DC-SIGN. Monocytes/macrophages and monocytoid DCs, but not plasmacytoid DCs, displayed significant increases in surface expression of Toll-like receptor 1 (TLR1), TLR2, and TLR4. Staining for CD45RO and CD27 revealed that lipopeptides preferentially recruited antigen-experienced T-cell subsets; despite their lack of antigenicity, these agonists induced marked T-cell activation, as evidenced by surface expression of CD69, CD25, and CD71. Lipopeptides also induced significant increases in interleukin 12 (IL-12), IL-10, gamma interferon, and most notably IL-6 without corresponding increases in serum levels of these cytokines. Although lipopeptides and EM lesional infiltrates shared many similarities, differences were noted in a number of immunologic parameters. These studies have provided in situ evidence for a prominent “lipoprotein effect” during human infection while at the same time helping to pinpoint aspects of the cutaneous response that are uniquely driven by spirochetal pathogens.
机译：在这项研究中，我们使用了表皮吸水泡技术和多参数流式细胞术，分析了人体志愿者皮内注射螺旋体脂蛋白合成类似物引起的细胞和细胞因子应答，并将应答与以前报道的患者进行了比较。偏头痛红斑（EM）。与外周血（PB）相比，脂蛋白来源于博雷尔氏疏螺旋体外表面蛋白C的N末端和梅毒螺旋体（emsp）的17-kDa脂蛋白（OspC-L和分别为17-L）引起浸润，该浸润富含单核细胞/巨噬细胞和树突状细胞（DC），但同时也包含大量百分比的嗜中性粒细胞和T细胞。单核细胞（CD11c + ）和浆细胞样（CD11c ？）DC被选择性地募集到皮肤中，其比例与PB中相似，但只有前者表达激活/成熟表面标记CD80，CD83和DC-SIGN。单核细胞/巨噬细胞和单核细胞DC，而不是浆细胞样DC，显示Toll样受体1（TLR1），TLR2和TLR4的表面表达显着增加。对CD45RO和CD27的染色表明，脂肽优先募集了抗原经历的T细胞亚群。尽管缺乏抗原性，这些激动剂仍能诱导显着的T细胞活化，如CD69，CD25和CD71的表面表达所证明的。脂肽还诱导白介素12（IL-12），IL-10，γ干扰素和最显着的IL-6显着增加，而这些细胞因子的血清水平没有相应增加。尽管脂肽和EM病灶浸润物具有许多相似之处，但在许多免疫学参数上仍存在差异。这些研究提供了原位证据，证明了人类感染过程中显着的“脂蛋白效应”，同时有助于查明由螺旋体病原体唯一驱动的皮肤反应方面。

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