TLR2和TLR7信号协同作用导致小鼠炎性反应增强和胚胎丢失率增高的机制研究  

Synergistic signaling between TLR2 and TLR7 signaling leads to amplification of inflammatory responses and increased murine embryo loss

作　　者：杨新颖[1] 李莉平[2] 王文静[1] 张旭淼[1] 林羿[1] 

机构地区：[1]上海交通大学医学院附属仁济医院妇产科学研究所,上海200127 [2]广州医学院附属广州市第一人民医院妇产科,广州510180

出　　处：《现代免疫学》2013年第2期100-106,共7页Current Immunology

基　　金：国家自然科学基金资助(31171439;81200478)

摘　　要：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 pathogens and activate host innate immune responses. TLR2 responds to Gram- positive bacteria and components of their cell walls. TLR7 responds to single-stranded RNA produced by viruses. A mouse macrophage cell line （RAW264.7） and freshly obtained murine peritoneal macrophages were treated in cell culture with TLR2 ligand peptidoglycan （PGN） or TLR7 ligand R837 alone, or in combination. A mouse model of embryo resorption induced by TLR ligands was used to evaluate in vivo effects. Stimulation of macrophages with both ligands resulted in synergistic effect on production of inflammatory cytokines IL-1β, CCL5 and TNF-α. Simultaneous administration of both PGN and R837 to pregnant mice also produced dramatic synergy in the occurrence of embryo loss. Neutralizing antibodies against IL-1β, CCL5 and TNF-α significantly reduced embryo resorption rate in PGN-and R837-treated mice. These results support a synergistic effect of simultaneous bacterial and viral infection on abortion, and IL-1β, CCL5 and TNF-α may be involved in this course.

关 键 词：动物模型 细胞信息转导 免疫调节 免疫识别 妊娠 

分 类 号：R392.11[医药卫生—免疫学]