Neuro-immune mediated control of mucosal immunity

项目总结： 宿主-微生物的相互作用是健康的关键决定因素。肠粘膜提供了几种 截然不同的相互重叠的机制，共同发挥作用，以降低病原体 接近身体。这些保护机制主要是由专门的肠道提供的 能够产生粘液和杀菌抗菌肽的上皮细胞。虽然它已经很久了 众所周知，神经递质控制着这一过程，人们曾假设这些物质起源于 神经元。最近，我们发现了一种独特的B细胞和T细胞亚群，它们可以产生 神经递质乙酰胆碱，并在肠道细菌感染期间专门招募。 这个项目的总体目标是确定这些独特的B细胞和T细胞的作用并阐明 所引发的保护机制。这将通过使用中和抗体和 条件基因敲除小鼠破译这些细胞在感染过程中的作用(SA1)。确定这些是否 B细胞和T细胞通过增加粘液的产生和释放来保护宿主 SA2.这些细胞诱导抗菌肽表达的能力也将在SA2中进行评估。 总之，这些拟议的研究将破译一种独特的免疫细胞群体对 粘膜宿主防御。

Project summary: Host-microbial interactions are a critical determinant of health. The intestinal mucosa provides serval distinct overlapping mechanisms that function together in concert to reduce the ability of pathogens to gain access to the body. These protective mechanisms are largely provided by specialized intestinal epithelial cells that can produce mucous and bactericidal antimicrobial peptides. While it has long been known that neurotransmitters control this process, it had been assumed that these originated from neurons. Recently we have identified a unique subset of B- and T-cells that produce the neurotransmitter acetylcholine, and that are specifically recruited during enteric bacterial infection. The overall goals of this project are to determine the role of these unique B- and T-cells and elucidate the mechanisms of protection that are elicited. This will be achieved by using neutralizing antibodies and conditional knockout mice to decipher the role of these cells during infection (SA1). Determining if these B- and T-cells are protective to the host by increasing mucous production and release will be assessed in SA2. The ability of these cells to induce expression of antimicrobial peptides will also be assessed in SA2. Together, these proposed studies will decipher the contribution of a unique immune cell population to mucosal host defense.