Toll样受体2（TLR2）与Toll样受体4（TLR4）和Toll样受体9（TLR9）协同作用，以诱导髓样分化因子88（MyD88）依赖性的脾脏细胞因子和趋化因子对肺炎链球菌的应答。
TLR2 synergizes with both TLR4 and TLR9 for induction of the MyD88-dependent splenic cytokine and chemokine response to Streptococcus pneumoniae.
作者信息
Lee Katherine S, Scanga Charles A, Bachelder Eric M, Chen Quanyi, Snapper Clifford M
机构信息
Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
出版信息
Cell Immunol. 2007 Feb;245(2):103-10. doi: 10.1016/j.cellimm.2007.04.003. Epub 2007 May 22.
We previously demonstrated that induction of splenic cytokine and chemokine secretion in response to Streptococcus pneumoniae (Pn) is MyD88-, but not critically TLR2-dependent, suggesting a role for additional TLRs. In this study, we investigated the role of TLR2, TLR4, and/or TLR9 in mediating this response. We show that a single deficiency in TLR2, TLR4, or TLR9 has only modest, selective effects on cytokine and chemokine secretion, whereas substantial defects were observed in TLR2(-/-)xTLR9(-/-) and TLR2(-/-)xTLR4(-/-) mice, though not as severe as in MyD88(-/-) mice. Chloroquine, which inhibits the function of intracellular TLRs, including TLR9, completely abrogated detectable cytokine and chemokine release in spleen cells from TLR2(-/-)xTLR4(-/-) mice, similar to what is observed for mice deficient in MyD88. These data demonstrate significant synergy between TLR2 and both TLR4 and TLR9 for induction of the MyD88-dependent splenic cytokine and chemokine response to Pn.
我们先前证明，脾脏细胞因子和趋化因子对肺炎链球菌（Pn）应答的分泌诱导是依赖髓样分化因子88（MyD88）的，但并非严格依赖Toll样受体2（TLR2），这提示其他TLR发挥了作用。在本研究中，我们调查了TLR2、TLR4和/或TLR9在介导该应答中的作用。我们发现，TLR2、TLR4或TLR9单基因缺陷对细胞因子和趋化因子的分泌仅有适度的、选择性的影响，而在TLR2（-/-）×TLR9（-/-）和TLR2（-/-）×TLR4（-/-）小鼠中观察到了显著缺陷，尽管不如MyD88（-/-）小鼠严重。氯喹可抑制包括TLR9在内的细胞内TLR的功能，它完全消除了TLR2（-/-）×TLR4（-/-）小鼠脾细胞中可检测到的细胞因子和趋化因子释放，这与MyD88缺陷小鼠的情况相似。这些数据证明，TLR2与TLR4和TLR9之间在诱导对Pn的MyD88依赖的脾脏细胞因子和趋化因子应答方面存在显著协同作用。
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