中文摘要：研究应用奈瑟氏球菌外膜蛋白B、TLR2佐剂分析了细胞特异性MyD88信号在疫苗佐剂活性保持中的作用，并以CpG和与TLR无关的佐剂（MF59、铝）进行比较。研究发现，完整的MyD88信号对三种抗原呈递细胞中TLR佐剂的活性至关重要。已有研究报道，MyD88信号对B细胞和DC细胞中疫苗佐剂的作用。本研究通过试验证实，巨噬细胞特异性MyD88片段的敲除（Mac-MyD88(-/-)）会降低小鼠的免疫反应；TLR相关的佐剂是抗原呈递细胞中生发中心反应的诱导剂，采用TLR相关佐剂PorB或CpG免疫的Mac-MyD88(-/-)小鼠几乎缺失了生发中心， 而以MF59或铝为佐剂免疫不会产生这样的现象。本研究揭示了MyD信号在巨噬细胞中的重要作用，并应用于TLR配体佐剂中激发疫苗产生免疫反应。
 
外文摘要：Vaccines are critical in the fight against infectious diseases, and immune-stimulating adjuvants are essential for enhancing vaccine efficacy. However, the precise mechanisms of action of most adjuvants are unknown. There is an urgent need for customized and adjuvant formulated vaccines against immune evading pathogens that remain a risk today. Understanding the specific role of various cell types in adjuvant-induced protective immune responses is vital for an effective vaccine design. We have investigated the role of cell-specific MyD88 signaling in vaccine adjuvant activity in vivo, using Neisserial porin B (PorB), a TLR2 ligand-based adjuvant, compared with an endosomal TLR9 ligand (CpG) and toll-like receptor (TLR)-independent (alum, MF59) adjuvants. We found that intact MyD88 signaling is essential, separately, in all three antigen-presenting cell types [ B cells, macrophages, and dendritic cells (DCs)] for optimal TLR ligand-based adjuvant activity. The role of MyD88 signaling in B cell and DC in vaccine adjuvant has been previously investigated. In this study, we now demonstrate that the immune response was also reduced in mice with macrophage-specific MyD88 deletion (Mac-MyD88(-/-)). We demonstrate that TLR-dependent adjuvants are potent inducers of germinal center (GC) responses, but GCs are nearly absent in Mac-MyD88(-/-) mice following immunization with TLR-dependent adjuvants PorB or CpG, but not with TLR-independent adjuvants MF59 or alum. Our findings reveal a unique and here-to-for unrecognized importance of intact MyD88 signaling in macrophages, to allow for a robust vaccine-induced immune responses when TLR ligand-based adjuvants are used.
外文关键词：vaccines； MyD88； toll-like receptors； germinal centers； adjuvants； Neisseria meningitidis； porin B
作者：Mosaheb, MM; Reiser, ML; Wetzler, LM
作者单位：波士顿大学
期刊名称：FRONTIERS IN IMMUNOLOGY
期刊影响因子：5.695
出版年份：2017
出版刊次：3
点击下载：抗原呈递细胞中TOLL样受体配体佐剂必须具备完整的MyD88信号才能促进形成生发中心并产生抗体