Liu Tie, Matsuguchi Tetsuya, Tsuboi Naotake, Yajima Toshiki, Yoshikai Yasunobu
Laboratory of Host Defense, Research Institute for Disease Mechanism and Control, Nagoya University Graduate School of Medicine, Japan.
Infect Immun. 2002 Dec;70(12):6638-45. doi: 10.1128/IAI.70.12.6638-6645.2002.
We have previously reported that differences in early production of interleukin 12 (IL-12) by dendritic cells (DC) underlies the difference between the susceptibilities to Listeria monocytogenes of C57BL/6 and BALB/c mice. To elucidate mechanisms for the different abilities of DC to produce cytokine in C57BL/6 and BALB/c mice, we examined Toll-like receptor (TLR) expression by DC and their responses in vitro to known microbial ligands for TLRs. We found that DC isolated from the spleens of naive C57BL/6 mice preferentially expressed TLR9 mRNA, whereas DC from naive BALB/c mice strongly expressed TLR2, -4, -5, and -6 mRNAs. C57BL/6 DC produced a higher level of IL-12p40 in response to the ligands for TLR4 (lipopolysaccharide), TLR2 (lipoprotein), and TLR9 (CpG), whereas BALB/c DC responded to these ligands by producing a larger amount of monocyte chemoattractant protein 1. C57BL/6 DC expressed higher levels of CD40 and Stat4 than BALB/c DC did, suggesting that naive C57BL/6 mice contained more-mature subsets of DC than naive BALB/c mice. Differences in reactivities of DC to microbial molecules through TLRs may be associated with susceptibility and resistance to Listeria infection in BALB/c and C57BL/6 mice.
我们之前曾报道,树突状细胞(DC)早期产生白细胞介素12(IL-12)的差异是C57BL/6和BALB/c小鼠对单核细胞增生李斯特菌易感性差异的基础。为了阐明C57BL/6和BALB/c小鼠中DC产生细胞因子能力不同的机制,我们检测了DC的Toll样受体(TLR)表达及其在体外对已知TLR微生物配体的反应。我们发现,从未经处理的C57BL/6小鼠脾脏中分离的DC优先表达TLR9 mRNA,而未经处理的BALB/c小鼠的DC强烈表达TLR2、-4、-5和-6 mRNA。C57BL/6 DC对TLR4(脂多糖)、TLR2(脂蛋白)和TLR9(CpG)的配体产生更高水平的IL-12p40,而BALB/c DC对这些配体的反应是产生大量单核细胞趋化蛋白1。C57BL/6 DC比BALB/c DC表达更高水平的CD40和Stat4,这表明未经处理的C57BL/6小鼠比未经处理的BALB/c小鼠含有更成熟的DC亚群。DC通过TLR对微生物分子反应性的差异可能与BALB/c和C57BL/6小鼠对李斯特菌感染的易感性和抗性有关。