中文摘要：本研究重点分析了人型支原体与人树突状细胞的互作作用，支原体脂蛋白参与激活宿主细胞、诱导细胞的免疫反应；从支原体角度看，文章首次发现人型支原体脂蛋白是一种大分子蛋白，并具有生物活性；从细胞角度看，研究报道了细胞中炎性体的激活过程，这一过程与机体的天然免疫应答反应相关。
 
外文摘要：Mycoplasma hominis lacks a cell wall, and lipoproteins anchored to the extracellular side of the plasma membrane are in direct contact with the host components. A Triton X-114 extract of M. hominis enriched with lipoproteins was shown to stimulate the production of interleukin-23 (IL-23) by human dendritic cells (hDCs). The inflammasome activation of the host cell has never been reported upon M. hominis infection. We studied here the interaction between M. hominis PG21 and hDCs by analyzing both the inflammation-inducing mycoplasmal lipoproteins and the inflammasome activation of the host cell. IL-23-inducing lipoproteins were determined using a sequential extraction strategy with two nondenaturing detergents, Sarkosyl and Triton X-114, followed by SDS-PAGE separation and mass spectrometry identification. The activation of the hDC inflammasome was assessed using PCR array and enzyme-linked immunosorbent assay (ELISA). We defined a list of 24 lipoproteins that could induce the secretion of IL-23 by hDCs, 5 with a molecular mass between 20 and 35 kDa and 19 with a molecular mass between 40 and 100 kDa. Among them, lipoprotein MHO_4720 was identified as potentially bioactive, and a synthetic lipopeptide corresponding to the N-terminal part of the lipoprotein was subsequently shown to induce IL-23 release by hDCs. Regarding the hDC innate immune response, inflammasome activation with caspase-dependent production of IL-1 beta was observed. After 24 h of coincubation of hDCs with M. hominis, downregulation of the NLRP3-encoding gene and of the adaptor PYCARD-encoding gene was noticed. Overall, this study provides insight into both protagonists of the interaction of M. hominis and hDCs. IMPORTANCE Mycoplasma hominis is a human urogenital pathogen involved in gynecologic and opportunistic infections. M. hominis lacks a cell wall, and its membrane contains many lipoproteins that are anchored to the extracellular side of the plasma membrane. In the present study, we focused on the interaction between M. hominis and human dendritic cells and examined both sides of the interaction, the mycoplasmal lipoproteins involved in the activation of the host cell and the immune response of the cell. On the mycoplasmal side, we showed for the first time that M. hominis lipoproteins with high molecular mass were potentially bioactive. On the cell side, we reported an activation of the inflammasome, which is involved in the innate immune response.
外文关键词：Mycoplasma hominis, human dendritic cells, lipoproteins, lipopeptide, inflammasome, PCR array, caspase, IL-1 beta, IL-23, interaction, innate response
作者：Goret, J; Beven, L; Faustin, B; Contin-Bordes, C; Le Roy, C; Claverol, S; Renaudin, H; Bebear, C; Pereyre, S
作者单位：美国波尔多大学
期刊名称：JOURNAL OF BACTERIOLOGY
期刊影响因子：3.143
出版年份：2017
出版刊次：8
点击下载：人型支原体PG21与人树突状细胞的互作：IL-23能诱导支原体脂蛋白和激活细胞炎性体