ISBN 9783843958165

978-3-8439-5816-5, Reihe Biologie

Anna Weigert
The contribution of metabolism to defense processes directed against Salmonella Typhimurium

143 Seiten, Dissertation Universität Erlangen-Nürnberg (2026), Hardcover, B5

Zusammenfassung / Abstract

The cellular metabolism critically shapes defense mechanisms against bacterial infections by regulating activation, differentiation, and immune responses of immune cells. In addition to host immune-responses, it also controls intracellular survival and replication of bacterial pathogens. Whereas the classic metabolic pathways involved in immune-responses have already been intensively studied, less is known about the role of unconventional metabolite such as neurotransmitters in bacterial infections. Especially enteric pathogens like Salmonella which replicates in the gastrointestinal tract are exposed to high concentrations of serotonin as approximately 90% of the body’s serotonin is produced in the gastrointestinal tract. Serotonin also plays an important role in the central nervous system and blood-coagulation. Recent studies have demonstrated that bacteria express surface-receptors which sense serotonin enabling adaptive responses to the host environmental. Moreover, immune cells including macrophages can take up serotonin, thereby influencing their activation state and antimicrobial effector functions. Serotonin reuptake inhibitors (SSRIs) are used as antidepressant medication which alters serotonin homeostasis and can also affect broader metabolic pathways. This aim of this study is to investigate how perturbations of the serotonin-metabolism, induced by serotonin supplementation or SSRIs treatment, influences intracellular survival of Salmonella in murine macrophages. Additionally, we aim to decipher the underlying mechanism by identifying changes of in the host’s and pathogen’s transcriptome using dual RNA-sequencing. Furthermore, metabolic alterations in macrophages are measured via mass spectrometry. To determine if the observed effects extend beyond the cellular level, in vivo experiments are conducted using a murine sepsis model. Finally, the cross-species relevance of our findings is evaluated by using human macrophages from healthy donors.