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

Datum: Montag, 2. Dezember 2013
Zeit: 17:00 Uhr
Ort: NW Fakultät, Erdgeschoß, HS 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.