Interplay of immune cells and bacteria in response to stimulation by stress hormones ins pigs

压力会损害免疫系统的活性，大大增加哺乳动物感染的风险。据充分记载，应激激素，即儿茶酚胺和糖皮质激素，在触发这些效应中起主要作用。应激激素也促进细菌病原体的生长，从而影响宿主和病原体。除了在儿茶酚胺存在下病原体的增强生长之外，这些分子通过与特定受体结合的细胞内途径激活，导致改变的基因表达，并且还可能产生毒力因子。这种界间信号传导是微内分泌学的一个重要方面，微内分泌学是一门新学科，迄今为止主要集中在人类及其细菌病原体上。尽管动物生产中最严重的威胁在于传染病（有可能影响牲畜和人类），但应激激素对宿主-病原体相互作用的影响在猪中的研究仍然不够。因此，本研究的一个目的是评估应激激素对免疫细胞和细菌的影响。基于我们的第一个体外实验，特别强调T细胞，我们将进行体内实验与插管猪，以进一步表征应激激素对免疫系统在完整的有机体的影响。此外，我们将描绘的影响，应激激素对两个重要的细菌物种（沙门氏菌和霍乱弧菌）。第二个主要目的是研究猪免疫细胞与细菌在应对应激激素挑战时的相互作用，这是一个新的研究问题，迄今为止不仅限于牲畜研究。我们的初步结果清楚地表明，无细胞上清液的应激反应刺激的细菌改变哺乳动物淋巴细胞的活性水平，但负责的作用的分子的化学性质是未知的。因此，我们将测试来自酵母刺激的S.鼠伤寒沙门氏菌（一种猪病原体）对猪的免疫细胞的作用，并通过最新技术分析活性级分以鉴定活性分子。平行地，将测试来自细菌刺激的霍乱弧菌细胞的上清液的级分。对猪不致病的霍乱弧菌作为对照，因为界间信号传导完全可能依赖于引起肠道感染的革兰氏阴性细菌中保守的组分。该项目将提供关于应激猪免疫调节可能的其他途径的新信息。这些结果对于基础研究以及畜牧业和福利都很重要，并可能产生新的营养或医疗干预方法，目的是提高细菌感染条件下应激猪的免疫防御能力。

Stress impairs the activity of the immune system and contributes significantly to the risk of infection in mammals. It is well documented that stress hormones, i.e. catecholamines and glucocorticoids, play a major role in triggering these effects. Stress hormones also promote the growth of bacterial pathogens and thus influence both the host and the pathogen. In addition to an enhanced growth of the pathogen in the presence of catecholamines, these molecules activate via binding to specific receptors intracellular pathways that lead to an altered gene expression and possibly also the production of virulence factors. This inter-kingdom signaling is one important aspect of microendocrinology, a new discipline which is so far mainly focused on humans and their bacterial pathogens. Despite the fact that the most serious threat in animal production lies in infectious diseases (with the potential to affect both livestock and humans), the effects of stress hormones on host-pathogen-interactions are nevertheless still insufficiently studied in pigs. One objective of this study is therefore to assess the influence of stress hormones on immune cells and bacteria. Based on our first in vitro experiments with particular emphasis on T cells, we will conduct in vivo experiments with catheterized pigs to further characterize the effects of stress hormones on the immune system in the intact organism. In addition, we will delineate the effect of stress hormones on two important bacterial species (Salmonella typhimurium and Vibrio cholerae). A second main aim is to investigate the interplay of porcine immune cells with bacteria in response to a challenge by stress hormones, a novel research question which is by far not limited to livestock research. Our preliminary results clearly demonstrate that cell-free supernatants of stress hormone-stimulated bacteria alter the activity levels of mammalian lymphocytes, but the chemical nature of the molecule(s) responsible for effect is yet unknown. We will thus test the effect of supernatant fractions from hormone-stimulated S. typhimurium, a pig pathogen, on immune cells of pigs and analyze active fractions by state-of-the-art techniques to identify the active molecule(s). In parallel, fractions from supernatants of hormone-stimulated V. cholerae cells will be tested. V. cholerae, which is not pathogenic to pigs, serves as a control since it is entirely possible that inter-kingdom signaling might rely on components conserved in gram-negative bacteria which cause gut infections. This project will provide novel information about possible additional pathways of immune modulation in stressed pigs. The results are important for basic research as well as for animal husbandry and welfare and may generate new approaches for nutritional or medical intervention, with the goal to improve the immune defense in stressed pigs under the condition of bacterial infection.