Rodet F, Tasiemski A, Boidin-Wichlacz C, Van Camp C, Vuillaume C, Slomianny C, Salzet M
Inserm U-1192, Laboratoire de Protéomique, Réponse Inflammatoire, Spectrométrie de Masse (PRISM), Université de Lille 1, Cité Scientifique, 59655 Villeneuve D'Ascq, France.
Inserm U-1003, Equipe labellisée par la Ligue Nationale contre le cancer, Laboratory of Excellence, Ion Channels Science and Therapeutics, Université Lille 1, Cité Scientifique, 59655 Villeneuve d'Ascq, France.
Sci Rep. 2015 Apr 16;5:9624. doi: 10.1038/srep09624.
Unlike mammals, the CNS of the medicinal leech can regenerate damaged neurites, thus restoring neural functions after lesion. We previously demonstrated that the injured leech nerve cord is able to mount an immune response promoting the regenerative processes. Indeed neurons and microglia express sensing receptors like Hm-TLR1, a leech TLR ortholog, associated with chemokine release in response to a septic challenge or lesion. To gain insights into the TLR signaling pathways involved during these neuroimmune responses, members of the MyD88 family were investigated. In the present study, we report the characterization of Hm-MyD88 and Hm-SARM. The expression of their encoding gene was strongly regulated in leech CNS not only upon immune challenge but also during CNS repair, suggesting their involvement in both processes. This work also showed for the first time that differentiated neurons of the CNS could respond to LPS through a MyD88-dependent signalling pathway, while in mammals, studies describing the direct effect of LPS on neurons and the outcomes of such treatment are scarce and controversial. In the present study, we established that this PAMP induced the relocalization of Hm-MyD88 in isolated neurons.
与哺乳动物不同，药用水蛭的中枢神经系统（CNS）能够再生受损的神经突，从而在损伤后恢复神经功能。我们之前证明，受伤的水蛭神经索能够引发促进再生过程的免疫反应。实际上，神经元和小胶质细胞表达传感受体，如Hm-TLR1，一种水蛭TLR直系同源物，在受到败血症攻击或损伤时会伴随趋化因子释放。为了深入了解这些神经免疫反应过程中涉及的TLR信号通路，我们对MyD88家族成员进行了研究。在本研究中，我们报告了Hm-MyD88和Hm-SARM的特征。它们编码基因的表达不仅在免疫攻击时，而且在中枢神经系统修复过程中，在水蛭中枢神经系统中都受到强烈调控，表明它们参与了这两个过程。这项工作还首次表明，中枢神经系统的分化神经元可以通过MyD88依赖的信号通路对脂多糖（LPS）作出反应，而在哺乳动物中，描述LPS对神经元的直接作用及其治疗结果的研究很少且存在争议。在本研究中，我们确定这种病原体相关分子模式（PAMP）会诱导Hm-MyD88在分离的神经元中重新定位。
