The team led by Dr. Karsten Hiller, director of the Metabolomics Group at LCSB, and Dr. Alessandro Michelucci wanted to examine how the brain reacts if an immune response is triggered there. For this purpose, the scientists brought a microglial cell culture into contact with specific constituents of bacterial membranes. The microglial responded by producing a mixture of metabolic products.

The researchers analysed the individual metabolic constituents of this mixture and found that itaconic acid was an important component of the mixture. Subsequent genetic analyses showed that the so-called immune-responsive gene 1 (IRG1) is able to encode a specific enzyme that produces itaconic acid, a function that gene was not previously known to have.

Itaconic acid plays an important role in the killing of bacteria by macrophages, the large phagocyte cells of the immune system. As Dr. Karsten Hiller explained in a press release, the microorganisms are able to survive by using a special metabolic pathway called the glyoxylate shunt. Itaconic acid helps the macrophages to block this pathway and completely kill the bacteria.

The researchers have published their findings in the scientific journal PNAS:
Michelucci, A., Cordes, T., Ghelfi, J., Pailot, A., Reiling, N., Goldmann, O., Binz, T., Wegner, A., Tallam,
A., Rausell, A., Buttini, M., Linster, C. L., Medina, E., Balling, R. & Karsten Hiller (2013): Immune-
responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. PNAS 110/19: 7820–7825. http://www.pnas.org/content/110/19/7820.long

Contact:
Dr. Karsten Hiller
karsten.hiller[at]uni.lu,
Phone + 352 46 66 44 6136

More information: http://wwwen.uni.lu/lcsb/news_events/lcsb_discovers_endogenous_antibiotic_in_the_brain