How metabolism impacts the immune system
For decades, immunology and metabolism were separate fields of research. In recent years, these fields have moved toward each other and the metabolism of the immune system has become a highly active research field.
The so-called metabolome analysis captures all small molecules of a cell at a certain point in time. Karsten Hiller, metabolome specialist, investigated the metabolism of macrophages already during his stay at the Luxembourg Centre for Systems Biomedicine. His research group in Luxembourg discovered that these immune cells contain unusually high concentrations of itaconic acid, a previously poorly studied molecule. Collaborating with Eva Medina from the HZI and other partners, the researchers determined the enzyme that is responsible for the production of itaconic acid.
Further studies showed that itaconic acid acts as an endogenous antibiotic in that it kills the bacteria that are taken up by the macrophages. In July 2016, Karsten Hiller accepted an appointment at the Technische Universität Braunschweig. In addition to this position, he is also a department head at the HZI working in the Braunschweig Integrated Centre of Systems Biology. Meanwhile, his doctoral student, Yannic Nonnenmacher, developed and applied a special procedure to observe that itaconic acid inhibits an enzyme of the citrate cycle directly in mitochondria – i.e. the power plants – of macrophages. This inhibition leads to an increase in the amounts of succinate – a metabolite, which plays a crucial role in the re-programming of macrophage metabolism. Therefore, itaconic acid is obviously an important link between metabolism and the immune system.
Text: Yannic Nonnenmacher, Karsten Hiller und Ida Retter