Nakamura Kiwamu, Miyagi Kazuya, Koguchi Yoshinobu, Kinjo Yuki, Uezu Kaori, Kinjo Takeshi, Akamine Morikazu, Fujita Jiro, Kawamura Ikuo, Mitsuyama Masao, Adachi Yoshiyuki, Ohno Naohito, Takeda Kiyoshi, Akira Shizuo, Miyazato Akiko, Kaku Mitsuo, Kawakami Kazuyoshi
Department of Medicine and Therapeutics, Control and Prevention of Infectious Diseases, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
FEMS Immunol Med Microbiol. 2006 Jun;47(1):148-54. doi: 10.1111/j.1574-695X.2006.00078.x.
The present study was designed to elucidate the role of Toll-like receptor (TLR) 2 and TLR4 in the host response to Cryptococcus neoformans. Both TLR2 knockout (KO) and TLR4KO mice produced interleukin-1beta (IL-1beta), IL-6, IL-12p40 and tumor necrosis factor-alpha (TNF-alpha) in sera and cleared this fungal pathogen from infected lungs at a comparable level to control littermate (LM) mice. Synthesis of these cytokines was not significantly different in the lungs of these KO mice and LM mice, although IL-1beta, IL-6 and IL-12p40 tended to be lower in TLR2KO, but not TLR4KO, mice than in controls. In addition, there was no significant reduction detected in the synthesis of IL-12 and TNF-alpha by bone marrow-derived dendritic cells from TLR2KO and TLR4KO mice upon stimulation with live yeast cells. Finally, HEK293 cells expressing either TLR2/dectin-1 or TLR4/MD2/CD14 did not respond to C. neoformans in the activation of nuclear factor kappa B (NFkappaB) detected by a luciferase assay. Our results suggest that TLR2 and TLR4 do not or only marginally contribute to the host and cellular response to this pathogen.
本研究旨在阐明Toll样受体（TLR）2和TLR4在宿主对新型隐球菌反应中的作用。TLR2基因敲除（KO）小鼠和TLR4基因敲除小鼠血清中均产生白细胞介素-1β（IL-1β）、IL-6、IL-12p40和肿瘤坏死因子-α（TNF-α），并且从感染的肺中清除这种真菌病原体的水平与对照同窝小鼠（LM）相当。这些基因敲除小鼠和对照同窝小鼠肺中这些细胞因子的合成没有显著差异，尽管TLR2基因敲除小鼠（而非TLR4基因敲除小鼠）中的IL-1β、IL-6和IL-12p40往往低于对照。此外，用活酵母细胞刺激后，来自TLR2基因敲除小鼠和TLR4基因敲除小鼠的骨髓来源树突状细胞合成IL-12和TNF-α没有显著减少。最后，通过荧光素酶测定法检测，表达TLR2/小清蛋白-1或TLR4/MD2/CD14的人胚肾293细胞在新型隐球菌激活核因子κB（NFκB）时没有反应。我们的结果表明，TLR2和TLR4对宿主和细胞对这种病原体的反应没有贡献或仅有微小贡献。
