Hashimoto Masahito, Tawaratsumida Kazuki, Kariya Hiroyuki, Kiyohara Ai, Suda Yasuo, Krikae Fumiko, Kirikae Teruo, Götz Friedrich
Department of Nanostructure and Advanced Materials, Kagoshima University, Kagoshima, Japan.
J Immunol. 2006 Sep 1;177(5):3162-9. doi: 10.4049/jimmunol.177.5.3162.
Lipoteichoic acid (LTA) derived from Staphylococcus aureus is reported to be a ligand of TLR2. However, we previously demonstrated that LTA fraction prepared from bacterial cells contains lipoproteins, which activate cells via TLR2. In this study, we investigated the immunobiological activity of LTA fraction obtained from S. aureus wild-type strain, lipoprotein diacylglycerol transferase deletion (delta lgt) mutant, which lacks palmitate-labeled lipoproteins, and its complemented strain and evaluated the activity of LTA molecule. LTA fraction was prepared by butanol extraction of the bacteria followed by hydrophobic interaction chromatography. Although all LTA fractions activated cells through TLR2, the LTA from delta lgt mutant was 100-fold less potent than those of wild-type and complemented strains. However, no significant structural difference in LTA was observed in NMR spectra. Further, alanylation of LTA molecule showed no effect in immunobiological activity. These results showed that not LTA molecule but lipoproteins are dominant immunobiologically active TLR2 ligand in S. aureus.
据报道,源自金黄色葡萄球菌的脂磷壁酸(LTA)是Toll样受体2(TLR2)的配体。然而,我们之前证明,从细菌细胞制备的LTA组分含有脂蛋白,这些脂蛋白可通过TLR2激活细胞。在本研究中,我们调查了从金黄色葡萄球菌野生型菌株、缺乏棕榈酸酯标记脂蛋白的脂蛋白二酰基甘油转移酶缺失(delta lgt)突变体及其互补菌株获得的LTA组分的免疫生物学活性,并评估了LTA分子的活性。通过用丁醇提取细菌,然后进行疏水相互作用色谱法来制备LTA组分。尽管所有LTA组分均通过TLR2激活细胞,但来自delta lgt突变体的LTA的效力比野生型和互补菌株的LTA低100倍。然而,在核磁共振光谱中未观察到LTA有明显的结构差异。此外,LTA分子的丙氨酰化对免疫生物学活性没有影响。这些结果表明,在金黄色葡萄球菌中,具有免疫生物学活性的主要TLR2配体不是LTA分子,而是脂蛋白。