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，并极大地增加哺乳动物感染的风险。众所周知，压力荷尔蒙，即儿茶酚胺和糖皮质激素，在触发这些效应方面发挥了重要作用。应激激素也促进细菌病原体的生长，从而影响寄主和病原体。除了在儿茶酚胺存在的情况下促进病原体的生长外，这些分子还通过与特定的受体结合激活细胞内途径，导致基因表达改变，并可能产生毒力因子。这种跨王国的信号是微内分泌学的一个重要方面，这是一门到目前为止主要专注于人类及其细菌病原体的新学科。尽管动物生产中最严重的威胁是传染病(有可能影响牲畜和人)，但应激激素对宿主-病原体-相互作用的影响在猪身上仍然没有得到充分的研究。因此，这项研究的一个目标是评估应激激素对免疫细胞和细菌的影响。在我们首次以T细胞为重点的体外实验的基础上，我们将对插管的猪进行体内实验，以进一步表征应激激素对完整生物体免疫系统的影响。此外，我们还将描述应激激素对两个重要细菌物种(鼠伤寒沙门氏菌和霍乱弧菌)的影响。第二个主要目的是调查猪免疫细胞与细菌之间的相互作用，以应对应激激素的挑战，这是一个新的研究问题，到目前为止并不局限于家畜研究。我们的初步结果清楚地表明，应激激素刺激细菌的无细胞培养上清改变了哺乳动物淋巴细胞的活动水平，但负责这种影响的分子(S)的化学性质尚不清楚。因此，我们将测试激素刺激的猪伤寒沙门氏菌上清部分对猪免疫细胞的影响，并通过最先进的技术分析活性部分以鉴定活性分子(S)。与此同时，来自激素刺激的霍乱弧菌细胞上清液的组分将被测试。霍乱弧菌对猪没有致病性，作为对照，因为跨王国信号可能完全可能依赖于导致肠道感染的革兰氏阴性细菌中保守的成分。该项目将提供有关应激猪免疫调节可能的其他途径的新信息。这一结果对基础研究、畜牧业和福利具有重要意义，并可能为营养或医学干预提供新的途径，目的是提高应激猪在细菌感染条件下的免疫防御能力。

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.