Nakamura Kiwamu, Miyazato Akiko, Koguchi Yoshinobu, Adachi Yoshiyuki, Ohno Naohito, Saijo Shinobu, Iwakura Yoichiro, Takeda Kiyoshi, Akira Shizuo, Fujita Jiro, Ishii Keiko, Kaku Mitsuo, Kawakami Kazuyoshi
Department of Infection Control and Laboratory Diagnostics, Internal Medicine, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Microbes Infect. 2008 Aug-Sep;10(10-11):1223-7. doi: 10.1016/j.micinf.2008.06.011. Epub 2008 Jul 3.
The present study was designed to elucidate the role of TLR2, TLR4 and dectin-1 in the production of IL-12p40 by bone marrow-derived dendritic cells (BM-DCs) infected with Penicillium marneffei. IL-12p40 production was almost completely abrogated in BM-DCs from TLR2 gene-knockout (KO) and MyD88KO mice, but not from TLR4-defective C3H/HeJ mice compared to those from control mice. Furthermore, BM-DCs from dectin-1KO mice faintly produced IL-12p40 upon stimulation with this fungus. Using a luciferase reporter assay, P. marneffei activated NF-kappaB in HEK293 cells transfected with the TLR2 gene, but not with the dectin-1 gene, and their co-transfection did not lead to further increase in this response. These results indicate that TLR2 and dectin-1 are essential in sensing P. marneffei for the activation of BM-DCs.
本研究旨在阐明Toll样受体2（TLR2）、Toll样受体4（TLR4）和树突状细胞特异性C型凝集素-1（dectin-1）在马尔尼菲青霉菌感染的骨髓来源树突状细胞（BM-DC）产生白细胞介素-12p40（IL-12p40）过程中的作用。与对照小鼠来源的BM-DC相比，TLR2基因敲除（KO）小鼠和髓样分化因子88（MyD88）KO小鼠来源的BM-DC中IL-12p40的产生几乎完全被消除，但TLR4缺陷的C3H/HeJ小鼠来源的BM-DC中IL-12p40的产生并未被消除。此外，dectin-1 KO小鼠来源的BM-DC在用这种真菌刺激后微弱地产生IL-12p40。使用荧光素酶报告基因检测法，马尔尼菲青霉菌在转染了TLR2基因的人胚肾293（HEK293）细胞中激活核因子κB（NF-κB），但在转染了dectin-1基因的HEK293细胞中未激活NF-κB，并且它们的共转染并未导致该反应进一步增加。这些结果表明，TLR2和dectin-1在识别马尔尼菲青霉菌以激活BM-DC中起关键作用。
