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

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.

DFG Programme Research Grants