Applequist Steven E, Wallin Robert P A, Ljunggren Hans-Gustaf
Microbiology and Tumor Biology Center, Karolinska Institutet, 171 77 Stockholm, Sweden.
Int Immunol. 2002 Sep;14(9):1065-74. doi: 10.1093/intimm/dxf069.
Pattern recognition receptors (PRR) play an important roll in immediate responses to different conserved molecules produced by microbes. In this paper we describe the cloning of the mouse homolog of Toll-like receptor (TLR) 3, and present an analysis of the expression of this gene in innate and adaptive immune cell lines. We also performed a broad expression study on these cells of other TLR, including TLR family members whose expression pattern is not known, i.e. TLR7. The analysis was done in order to understand, and possibly predict, how innate and adaptive immune cells respond to microbial pattern antigens. This first large-scale analysis of immune cell TLR expression in the mouse reveals that cells of the innate immune system express a broader number of TLR than cells of the adaptive immune system, supporting preconceptions concerning the hierarchy of immune cells involved in direct pathogen recognition. Additionally, the expression of TLR transcripts by mast cells, neutrophils and microglial cells observed here suggests that pathogen-associated molecular pattern molecules could induce activation of these cells through TLR. Finally, the mouse homolog of human TLR3 identified here may, like its human counterpart, be an exceptional TLR molecule due to its lack of a conserved proline residue seen to be involved in existing TLR signaling capabilities found in other TLR family members.
模式识别受体(PRR)在对微生物产生的不同保守分子的即时反应中发挥着重要作用。在本文中,我们描述了小鼠Toll样受体(TLR)3同源物的克隆,并对该基因在先天性和适应性免疫细胞系中的表达进行了分析。我们还对这些细胞中的其他TLR进行了广泛的表达研究,包括那些表达模式未知的TLR家族成员,即TLR7。进行该分析是为了了解并可能预测先天性和适应性免疫细胞如何对微生物模式抗原作出反应。对小鼠免疫细胞TLR表达的首次大规模分析表明,先天性免疫系统的细胞比适应性免疫系统的细胞表达更多种类的TLR,这支持了关于参与直接病原体识别的免疫细胞层次结构的先入之见。此外,此处观察到肥大细胞、中性粒细胞和小胶质细胞中TLR转录本的表达表明,病原体相关分子模式分子可能通过TLR诱导这些细胞的激活。最后,此处鉴定出的人类TLR3的小鼠同源物可能与其人类对应物一样,是一种特殊的TLR分子,因为它缺乏一个保守的脯氨酸残基,而该残基被认为参与了其他TLR家族成员现有的TLR信号传导能力。