NBO, INRA, Univ Paris-Saclay, 78350 Jouy-en-Josas, France.
NBO, INRA, Univ Paris-Saclay, 78350 Jouy-en-Josas, France; Université de Versailles Saint-Quentin en Yvelines, 78000 Versailles, France.
Brain Behav Immun. 2019 Jul;79:274-283. doi: 10.1016/j.bbi.2019.02.012. Epub 2019 Feb 15.
At the interface of the environment and the nervous system, the olfactory mucosa (OM) is a privileged pathway for environmental toxicants and pathogens towards the central nervous system. The OM is known to produce antimicrobial and immunological components but the mechanisms of action of the immune system on the OM remain poorly explored. IL-17c is a potent mediator of respiratory epithelial innate immune responses, whose receptors are highly expressed in the OM of mice. We first characterized the presence of the IL-17c and its receptors in the OM. While IL-17c was weakly expressed in the control condition, it was strongly expressed in vivo after intranasal administration of polyinosinic-polycytidylic (Poly I:C), a Toll Like Receptor 3 agonist, mimicking a viral infection. Using calcium imaging and electrophysiological recordings, we found that IL-17c can effectively activate OM cells through the release of ATP. In the longer term, intranasal chronic instillations of IL-17c increased the cellular dynamics of the epithelium and promoted immune cells infiltrations. Finally, IL-17c decreased cell death induced by Poly(I:C) in an OM primary culture. The OM is thus a tissue highly responsive to immune mediators, proving its central role as a barrier against airway pathogens.
在环境与神经系统的交界处,嗅黏膜(OM)是环境毒物和病原体进入中枢神经系统的一条重要途径。已知 OM 能够产生抗菌和免疫成分,但免疫系统在 OM 上的作用机制仍未得到充分探索。IL-17c 是呼吸道上皮固有免疫反应的有力介质,其受体在小鼠 OM 中高度表达。我们首先研究了 OM 中 IL-17c 及其受体的存在情况。在对照条件下,IL-17c 的表达较弱,但在经鼻给予 Toll 样受体 3 激动剂聚肌苷酸-聚胞苷酸(Poly I:C)后,其表达明显增强,模拟病毒感染。通过钙成像和电生理记录,我们发现 IL-17c 可以通过释放 ATP 有效激活 OM 细胞。在长期影响方面,IL-17c 经鼻慢性滴注可增加上皮细胞的动力学,并促进免疫细胞浸润。最后,IL-17c 降低了 OM 原代培养物中 Poly(I:C)诱导的细胞死亡。因此,OM 是一种对免疫介质高度敏感的组织,证明了其作为气道病原体屏障的核心作用。