Sato Ayuko, Linehan Melissa M, Iwasaki Akiko
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17343-8. doi: 10.1073/pnas.0605102103. Epub 2006 Nov 3.
Dendritic cells (DCs) express multiple Toll-like receptors (TLR) in distinct cellular locations. Herpes simplex viruses (HSV) have been reported to engage both the surface TLR2 and intracellular TLR9 in conventional DCs. However, the contributions of these TLRs in recognition of HSV and the induction of proinflammatory cytokines in DCs remain unclear. Here, we demonstrate that a rare population of HSV, both in laboratory strains and in primary clinical isolates from humans, has the capacity to activate TLR2. This virus population is recognized through both TLR2 and TLR9 for the induction of IL-6 and IL-12 secretion from bone marrow-derived DCs. Further, we describe a previously uncharacterized pathway of viral recognition in which TLR2 and TLR9 are engaged in sequence within the same DC. Live viral infection results in two additional agonists of TLR2 and TLR9. These results indicate that in cells that express multiple TLRs, pathogens that contain multiple pathogen-associated molecular patterns can be detected in an orchestrated sequence and suggest that the innate immune system in DCs is optimized to linking uptake and degradation of pathogens to microbial recognition.
树突状细胞（DCs）在不同的细胞位置表达多种Toll样受体（TLR）。据报道，单纯疱疹病毒（HSV）可与传统DCs表面的TLR2和细胞内的TLR9结合。然而，这些TLR在识别HSV以及诱导DCs产生促炎细胞因子方面的作用仍不清楚。在此，我们证明，无论是实验室菌株还是来自人类的原发性临床分离株中的罕见HSV群体，都具有激活TLR2的能力。该病毒群体通过TLR2和TLR9被识别，从而诱导骨髓来源的DCs分泌IL-6和IL-12。此外，我们描述了一种以前未被描述的病毒识别途径，其中TLR2和TLR9在同一DC内按顺序发挥作用。活病毒感染会产生另外两种TLR2和TLR9激动剂。这些结果表明，在表达多种TLR的细胞中，含有多种病原体相关分子模式的病原体可以按精心编排的顺序被检测到，这表明DCs中的先天免疫系统经过优化，可将病原体的摄取和降解与微生物识别联系起来。
