P05

Overview:

Tuberculosis is one of the most common and important infections woldwide. In the first funding period we demonstrated that neutral sphingomyelinase 2 (Nsm, Smpd3) regulates the release of reactive oxygen species (ROS) in macrophages upon infection with Bacillus Calmette-Guérin (BCG). ROS in turn suppress autophagy in BCG-infected macrophages in vitro and in vivo; this suppression allows the pathogen to survive within macrophages. These findings indicate that the Nsm/ceramide system plays an important role in the pathogen’s attack on the host. We will now define signalling events that are regulated by the neutral sphingomyelinase and ceramide during the infection of macrophages with BCG. These insights will be applied to investigate molecular mechanism that mediate the formation of granuloma and, second, the killing of intracellular BCG by macrophages.

Publications:

Li C, Peng H, Japtok L, Seitz A, Riehle A, Wilker B, Soddemann M, Kleuser B, Edwards M, Lammas D, Zhang Y, Gulbins E, Grassmé H. (2016) Inhibition of neutral sphingomyelinase protects mice against systemic tuberculosis. Front. Biosci. 8:311-325.