Surface layer proteins from Clostridium difficile induce inflammatory and regulatory cytokines in human monocytes and dendritic cells
Surface layer proteins from Clostridium difficile induce inflammatory and regulatory cytokines in human monocytes and dendritic cells
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DOI：
10.1016/j.micinf.2006.07.009
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发表时间：
2006-09-01
影响因子：
5.8
通讯作者：
Mastrantonio, Paola
中科院分区：
文献类型：
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作者：
Ausiello, Clara Maria;Cerquetti, Marina;Mastrantonio, Paola
艰难梭菌是大多数抗生素相关性腹泻病例的病原体，主要通过毒素 A 和毒素 B 的活性发挥其病理作用。但鲜为人知的是，细菌的主要表面成分 S 层蛋白 (SLP) 在发病机制中可能发挥的作用。在这里，我们评估了 SLP 调节人类单核细胞和树突状细胞 (DC) 功能以及诱导炎症和调节性细胞因子、影响自然和适应性免疫反应的能力。为此，我们从临床分离株 C253 中提取了 SLP，并对其对免疫细胞的影响进行了表征。 SLP 诱导静息单核细胞释放大量白细胞介素 (IL)-1 β 和 IL-6 促炎细胞因子，诱导人单核细胞来源的 DC (MDDC) 成熟，并增强同种异体 T 细胞的增殖。 C253-SLP 处理的 MDDC 还分泌大量 IL-10 和 IL-12p70，并在初始 CD4 T 细胞中诱导混合 Th1/Th2 方向的免疫反应。总之，艰难梭菌 SLP 可能通过扰乱炎症和调节细胞因子的良好平衡来促进细菌的致病性。鉴于 SLP 可能用于针对高危患者的艰难梭菌感染的多组分疫苗中，这些数据也很有趣。 (c) 2006 年 Elsevier Masson SAS。版权所有。
Clostridium difficile, an etiological agent of most cases of antibiotic-associated diarrhea, exerts its pathological action mainly by the activity of toxin A and toxin B. Less known is the role that S-layer proteins (SLPs), predominant surface components of the bacterium, may play in pathogenesis. Here, we evaluate the ability of SLPs to modulate the function of human monocytes and dendritic cells (DC) and to induce inflammatory and regulatory cytokines, influencing the natural and adaptive immune response. To this aim, SLPs we're extracted from the clinical isolate C253 and characterized for their effects on immune cells. SLPs induced the release of elevated amounts of interleukin (IL)-1 beta and IL-6 pro-inflammatory cytokines by resting monocytes, induced maturation of human monocyte-derived DC (MDDC), and enhanced proliferation of allogeneic T cells. C253-SLP-treated MDDC also secreted large amounts of IL-10 and IL-12p70 and induced a mixed Th1/Th2 orientation of immune response in naive CD4 T cells. In conclusion, C. difficile SLPs may contribute to the pathogenicity of the bacterium by perturbing the fine balance of inflammatory and regulatory cytokines. These data are of interest also in the light of the possible use of SLPs in a multicomponent vaccine against C. difficile infections for high-risk patients. (c) 2006 Elsevier Masson SAS. All rights reserved.