Zychlinsky, Prof. Arturo
 Address: Max Planck Institute for Infection Biology Dept. Cellular Microbiology Campus Charité Mitte Charitéplatz 1 10117 Berlin Phone: +49 30 28460-300 Fax: +49 30 28460-301 This email address is being protected from spambots. You need JavaScript enabled to view it. WebsiteOur research focuses on the host-parasite interactions in acute inflammatory intestinal diseases caused by the Gram negative bacterium Shigella. Shigella is the causative agent of dysentery (shigellosis), a severe form of bloody diarrhea. Worldwide, an estimated 165 million cases of shigellosis occur annually resulting in at least 1.1 million deaths mainly among children. We use infections with Shigella flexneri, the most prevalent species, as a model system. We are especially interested in the following questions: (1) Bacterial induced inflammation and apoptosis. Shigella induces rapid macrophage apoptosis after it escapes from the phagosome into the cytoplasm of the macrophage. The bacteria inject Invasion Plasmid Antigen B (IpaB) which activates caspase-1. Casp-1 is a cysteine protease that has the dual function of activating apoptosis and cleaving the proinflammatory cytokines IL-1?? and IL-18. These two cytokines are essential to elicit the acute inflammation typical of dysentery. Apoptosis as a proinflammatory event is a common mechanism of pathogenesis among enterobacteria. (2) Toll Like Receptors (TLR). TLR sense bacteria and initiate an innate immune response. TLR2 transmits signals into the cell in response to bacterial lipoproteines (BLP), which are expressed by all prokaryotes. The characteristic N-terminal lipo-amino acid, N-acyl-S-diacylglyceryl cysteine, common to all BLPs, is necessary for TLR activation. Two different signaling cascades culminate either in activation of the transcriptional activator NF-kB or in apoptosis. (3) The resolution of bacterial infections. Neutrophils are phagocytic cells that kill bacteria efficiently and are crucial for the resolution of infections. In contrast to other cells, neutrophils prevent the escape of Shigella from phagocytic vacuoles in which the bacteria are killed. Neutrophil Elastase (NE) degrades virulence factors with high specificity destroying the Shigella invasion apparatus and trapping the bacteria in phagocytic vacuoles: NE also preferentially cleaves virulence factors of Salmonella and Yersinia. |
