PD Dr. Katharina HIEKE-KUBATZKY
UniversitätsKlinikum Heidelberg, Medizinische Mikrobiologie und Hygiene, Department für Infektiologie

Date: Monday, 2. December 2013
Time: 5.00 pm
Location: Faculty of Natural Sciences, ground floor, Lecture Room Green (403), Hellbrunnerstraße 34, 5020 Salzburg

Abstract
Toxigenic Pasteurella multocida strains produce the mitogenic protein toxin PMT (Pasteurella multocida Toxin), which enters mammalian host cells and subsequently causes constitutive activation of distinct G protein α subunits through deamidation of a glutamine residue required for GTP hydrolysis. Downstream, PMT stimulates several mitogenic signalling cascades such as the JAK (Janus kinase)-STAT (signal transducers and activators of transcription) pathway and is discussed to act as a carcinogen. We have shown previously that PMT causes the production of the pro-inflammatory cytokines IL-6, TNF-α and IL-1β from primary murine macrophages. IL-1β is a pluripotent cytokine and one of the most important mediators of inflammation. Synthesis of the precursor protein and processing into its bioactive form are tightly regulated, as disturbed control of IL-1β release can cause severe autoinflammatory diseases or can even promote cancer development. Many bacterial endo- and exotoxins are known to activate the inflammasome, a protein complex that initiates the maturation of inflammatory cytokines, which eventually induces pyroptosis, i.e. the programmed cell death of immune cells as a consequence of cell stress induced by inflammation. PMT induces IL-1β maturation in macrophages, without inducing apoptosis or pyroptosis, through a so far undescribed mechanism, independently of Caspase-1 and the inflammasome.