Kawli Trupti, Tan Man-Wah
Department of Genetics, Department of Microbiology and Immunology, and Program in Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.
Nat Immunol. 2008 Dec;9(12):1415-24. doi: 10.1038/ni.1672. Epub 2008 Oct 14.
Communication between the immune and nervous systems, each of which is able to react rapidly to environmental stimuli, may confer a survival advantage. However, precisely how the nervous system influences the immune response and whether neural modulation of immune function is biologically important are not well understood. Here we report that neuronal exocytosis of neuropeptides from dense core vesicles suppressed the survival of Caenorhabditis elegans and their clearance of infection with the human bacterial pathogen Pseudomonas aeruginosa. This immunomodulatory function was mediated by INS-7, an insulin-like neuropeptide whose induction was associated with Pseudomonas virulence. INS-7 secreted from the nervous system functioned in a non-cell autonomous way to activate the insulin pathway and alter basal and inducible expression of immunity-related genes in intestinal cells.
免疫系统和神经系统都能够对环境刺激迅速做出反应，它们之间的通讯可能带来生存优势。然而，神经系统究竟如何影响免疫反应，以及免疫功能的神经调节在生物学上是否重要，目前还不太清楚。在此，我们报告来自致密核心囊泡的神经肽的神经元胞吐作用抑制了秀丽隐杆线虫的存活及其对人类细菌病原体铜绿假单胞菌感染的清除。这种免疫调节功能由INS-7介导，INS-7是一种胰岛素样神经肽，其诱导与铜绿假单胞菌的毒力相关。从神经系统分泌的INS-7以非细胞自主的方式发挥作用，激活胰岛素信号通路，并改变肠道细胞中免疫相关基因的基础表达和诱导表达。
