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Toll样受体(Toll-like receptors,TLR)识别致病原并激活宿主固有免疫反应。其中TLR2可识别革兰氏阳性细菌的细胞壁成分,而TLR7可识别病毒所产生的单链RNA。本研究采用小鼠巨噬细胞株(RAW264.7)和新鲜获得的小鼠腹腔巨噬细胞体外培养体系,用TLR2配体肽聚糖(peptidoglycan,PGN)或TLR7配体R837单独或联合刺激,观察其刺激效应。此外,采用上述TLR配体诱导建立小鼠胚胎吸收模型,观察体内条件下TLR2和TLR7信息转导对妊娠结局的影响。结果显示,两种配体同时刺激可呈现协同效应,导致巨噬细胞表达炎性细胞因子IL-1β、CCL5和TNF-α的水平显著增高。同时注射PGN和R837可使孕鼠胚胎丢失率显著增高。而预先注射中和抗体可显著降低PGN和R837所引起的胚胎丢失率增高。这些结果提示,细菌和病毒同时感染可发挥协同效应导致流产的发生,而IL-1β、CCL5和TNF-α等可能参与这一过程。
Toll-like receptors (TLRs) recognize pathogenic agents and activate the host’s innate immune response. TLR2 recognizes the cell wall components of Gram-positive bacteria, while TLR7 recognizes single-stranded RNA produced by the virus. In this study, mouse macrophage cell line (RAW264.7) and fresh mouse peritoneal macrophages in vitro culture system with TLR2 ligand peptidoglycan (PGN) or TLR7 ligand R837 alone or in combination, Observe its stimulating effect. In addition, the mouse embryo uptake model was induced by using the above TLR ligand to observe the effect of TLR2 and TLR7 information transduction on pregnancy outcome in vivo. The results showed that simultaneous stimulation of both ligands showed a synergistic effect, leading to a significant increase in the levels of inflammatory cytokines IL-1β, CCL5 and TNF-α expressed by macrophages. Simultaneous injection of PGN and R837 significantly increased embryo loss in pregnant rats. Preinjection of neutralizing antibody significantly reduced the rate of embryo loss caused by PGN and R837. These results suggest that simultaneous bacterial and viral infection can play a synergistic effect leading to abortion, and IL-1β, CCL5 and TNF-α may participate in this process.