Institut de Biologie du Développement de Marseille-Luminy, CNRS UMR 6216/Aix-Marseille II University, Campus de Luminy, Marseille, France.
PLoS One. 2011 Feb 28;6(2):e17470. doi: 10.1371/journal.pone.0017470.
Toll and Toll-like receptors represent families of receptors involved in mediating innate immunity response in insects and mammals. Although Drosophila proteome contains multiple Toll paralogs, Toll-1 is, so far, the only receptor to which an immune role has been attributed. In contrast, every single mammalian TLR is a key membrane receptor upstream of the vertebrate immune signaling cascades. The prevailing view is that TLR-mediated immunity is ancient. Structural analysis reveals that Drosophila Toll-9 is the most closely related to vertebrate TLRs and utilizes similar signaling components as Toll-1. This suggests that Toll-9 could be an ancestor of TLR-like receptors and could have immune function. Consistently, it has been reported that over-expression of Toll-9 in immune tissues is sufficient to induce the expression of some antimicrobial peptides in flies. These results have led to the idea that Toll-9 could be a constitutively active receptor that maintain significant levels of antimicrobial molecules and therefore provide constant basal protection against micro-organisms. To test theses hypotheses, we generated and analyzed phenotypes associated with a complete loss-of-function allele of Toll-9. Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection.
Toll 和 Toll 样受体是参与昆虫和哺乳动物固有免疫反应的受体家族。尽管果蝇蛋白组包含多个 Toll 同源物，但迄今为止，Toll-1 是唯一被赋予免疫作用的受体。相比之下，每一种哺乳动物 TLR 都是脊椎动物免疫信号级联的关键膜受体。普遍的观点是 TLR 介导的免疫是古老的。结构分析表明，果蝇 Toll-9 与脊椎动物 TLR 最接近，并利用与 Toll-1 相似的信号成分。这表明 Toll-9 可能是 TLR 样受体的祖先，并可能具有免疫功能。一致地，已经报道 Toll-9 在免疫组织中的过表达足以诱导苍蝇中一些抗菌肽的表达。这些结果导致了这样一种观点，即 Toll-9 可能是一种持续激活的受体，它维持着抗菌分子的显著水平，从而提供对微生物的持续基础保护。为了验证这些假设，我们生成并分析了 Toll-9 完全缺失功能等位基因相关的表型。我们的结果表明，Toll-9 既不需要维持基础的抗微生物反应，也不需要对细菌感染产生有效的免疫反应。
