Metabolic maintenance of tissue integrity by macrophages

The research field Immunometabolism studies intracellular metabolic pathways in immune cells that affect their function. Principally, cells flexibly utilize the available energy substrates using different metabolic pathways. Recent findings highlight that the use of distinct metabolic pathways directly regulates immune cell function. For example, immune cells that are acutely activated during a bacterial infection in order to kill the pathogen, rely on fermentation as a metabolic pathway to break down sugar. In contrast, cells responsible for tissue repair after the infection is cleared, prefer respiration to break down sugar. To date it is not understood why immune cells switch metabolism and how this switch alters their function. Current knowledge of immune metabolism is based primarily on in vitro experiments. However, the metabolic environment in the cell culture dish differs largely from the conditions in our body and is also different in the individual organs. The concentration of glucose, for example, is 10 times lower in the lungs than in the blood, while fatty acid concentrations are greatly increased in the intestine and adipose tissue. According to the motto "You are what you eat," it is believed that the availability of nutrients in the tissues directly controls immune functions. Furthermore, it is assumed that a malfunction in these metabolic processes, underlies many diseases. Pharmacological intervention in the aberrant metabolic processes of immune cells offers new therapeutic approaches to treat chronic diseases. How these different metabolites influence immune function, and how they ensure the integrity of the respective organ, is completely unclear. In this SFB- project 7 researchers from Graz and Vienna aim to answer these questions together. Macrophages represent the ideal immune cells to study the role of immune metabolism in tissues. Macrophages are evolutionary ancient cells already present in the most primitive multicellular organisms. They play an essential role in maintaining tissue integrity by phagocytosing ("eating") old or diseased tissue cells or pathogenic microorganisms and viruses. Consequently, macrophages have learned to adapt to a wide variety of ingested metabolites, the metabolization of which in turn affects their immune function. The multidisciplinary team with expertise in metabolism, immunology, biochemistry, epigenetics, biophysics, and the microbiome will study the metabolic functions of macrophages specifically in the gut and adipose tissue. Animal models, patients and innovative organoid cultures will be used to study human diseases in these tissues in order to find new therapeutic targets for inflammatory bowel disease, cancer, obesity, or diabetes.