Mechanism of innate immune activation by intestinal distension

摘要 区分有害微生物和有益微生物的能力对有机体的生存至关重要。渐增 有证据表明，细菌定植引起的肠道扩张激活了广泛的先天免疫。 回应。我们认为肠道的微生物定植和腹胀可能被视为一种危险。 激活免疫战斗和逃跑反应的信号。这种先天免疫激活依赖于输入 来自肠道的，可以帮助识别广泛的微生物，并可以调节宿主 使用控制免疫动态平衡的神经肠轴的反应。这份提案描述了实验 旨在阐明神经系统可以感知宿主整体变化的机制 病原体感染期间的生理反应和协调先天免疫反应。使用线虫 秀丽线虫，我们已经证明了神经系统中的特定基因和神经元 动物控制免疫反应，表明来自不同神经元的细胞非自主信号可能起作用 在非神经组织上调节生物体水平的先天免疫反应。我们建议使用 各种分子和遗传技术来探索寄主变化的一般假设 细菌感染引起的生理反应触发针对细菌感染的先天免疫反应 在整个动物水平上由神经系统控制。

SUMMARY The ability to distinguish harmful and beneficial microbes is critical for the survival of an organism. Increasing evidence indicates that gut distension caused by bacterial colonization activates a broad innate immune response. We propose that microbial colonization and bloating of the intestine may be perceived as a danger signal that activates an immune fight-and-flight response. This innate immune activation depends on inputs from the intestine that can aid in the recognition of a broad range of microbes and can modulate host responses using a neural-gut axis that controls immune homeostasis. This proposal describes experiments designed to elucidate the mechanisms by which the nervous system may sense overall changes in host physiology during pathogen infections and coordinate innate immune responses. Using the nematode Caenorhabditis elegans, we have demonstrated that specific genes and neurons in the nervous system of the animal control immune responses, indicating that cell non-autonomous signals from different neurons may act on non-neural tissues to regulate innate immune responses at the organismal level. We propose the use of a variety of molecular and genetic techniques to explore the general hypothesis that alterations in host physiology caused by bacterial infections trigger innate immune responses against bacterial infections that are controlled at that whole animal level by the nervous system.