ANTHRAX. LF EF TRAF6 TAK1 MKK3,6 p38 Targets Stimulus Activator MKKK MKK MAPK Targets LT = PA + LF ET = PA + EF Zinc metalloprotease TRAF2 MEKK1,

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Presentation transcript:

ANTHRAX

LF EF TRAF6 TAK1 MKK3,6 p38 Targets Stimulus Activator MKKK MKK MAPK Targets LT = PA + LF ET = PA + EF Zinc metalloprotease TRAF2 MEKK1, NIK IKK  IBIB NF  B

RIP Caspase 8/10 Fas/ CD95 FADD DAXX FasL FADD TRADD TRAF2 Caspase 8/10 IKK IBIB NF  B IAP Caspase 3 TNF TNFR Bid Cyt C Caspase 6 Caspase 7 Apaf1 Caspase 9 PARP Lamin A Actin Fodrin Cell shrinkage/membrane blebbing DNA repair CAD ICAD DNA fragmentation Death-receptor Mediated Apoptosis DNA damage Cellular stress Initiator caspases 2, 8, 9,10 Executioner caspases 3, 6, 7 Pro-inflammatory caspases 1,11 DISC Bcl-2

Yersinia Mechanisms of TIII secretion-induced cytotoxicity: IpaB IL-1  IL-18 Shigella, Salmonella, and Yersinia Inflammation PMN’s Shigella LPS TLR4 CD14 1 NF-kB IKK 2 macrophage or macrophage-like cell (SipB-S.t.) Survival signals Inflammatory cyt. prod. Apoptosis Cell Death Caspase 1 Caspase 8 Inflammatory apoptosis “Pyroptosis”

Yersinia Mechanisms of TIII secretion-induced cytotoxicity: IpaB IL-1  IL-18 Shigella, Salmonella, and Yersinia Inflammation PMN’s Shigella LPS TLR4 CD14 1 NF-kB YopJ IKK 2 macrophage or macrophage-like cell (SipB-S.t.) Survival signals Inflammatory cyt. prod. Apoptosis Cell Death Caspase 1 Caspase 8 Inflammatory apoptosis “Pyroptosis” Immunologically silent

LPS, Hoechst (necrosis + apoptosis) NECROSIS vs. APOPTOSIS LPS, TUNEL (apoptosis) No LPS, Hoechst No LPS, TUNEL

DIC Hoechst Annexin V

LPS