Edwards Alexander D, Diebold Sandra S, Slack Emma M C, Tomizawa Hideyuki, Hemmi Hiroaki, Kaisho Tsuneyasu, Akira Shizuo, Reis e Sousa Caetano
Immunobiology Laboratory, Cancer Research UK, London Research Institute, London, GB.
Eur J Immunol. 2003 Apr;33(4):827-33. doi: 10.1002/eji.200323797.
Toll-like receptors (TLR) recognize microbial and viral patterns and activate dendritic cells (DC). TLR distribution among human DC subsets is heterogeneous: plasmacytoid DC (PDC) express TLR1, 7 and 9, while other DC types do not express TLR9 but express other TLR. Here, we report that mRNA for most TLR is expressed at similar levels by murine splenic DC sub-types, including PDC, but that TLR3 is preferentially expressed by CD8 alpha(+) DC while TLR5 and TLR7 are selectively absent from the same subset. Consistent with the latter, TLR7 ligand activates CD8 alpha(-) DC and PDC, but not CD8 alpha(+) DC as measured by survival ex vivo, up-regulation of surface markers and production of IL-12p40. These data suggest that the dichotomy in TLR expression between plasmacytoid and non-plasmacytoid DC is not conserved between species. However, lack of TLR7 expression could restrict the involvement of CD8 alpha(+) DC in recognition of certain mouse pathogens.
Toll样受体(TLR)可识别微生物和病毒模式并激活树突状细胞(DC)。TLR在人类DC亚群中的分布是不均一的:浆细胞样DC(pDC)表达TLR1、7和9,而其他DC类型不表达TLR9但表达其他TLR。在此,我们报道,包括pDC在内的小鼠脾脏DC亚群中,大多数TLR的mRNA表达水平相似,但TLR3在CD8α(+) DC中优先表达,而同一亚群中TLR5和TLR7选择性缺失。与后者一致,通过体外存活、表面标志物上调和IL-12p40产生检测发现,TLR7配体可激活CD8α(-) DC和pDC,但不能激活CD8α(+) DC。这些数据表明,浆细胞样DC和非浆细胞样DC之间TLR表达的二分法在不同物种间并不保守。然而,TLR7表达的缺失可能会限制CD8α(+) DC参与对某些小鼠病原体的识别。