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ANTHRAX

ANTHRAX. Stimulus. Activator. MKKK. MKK. TRAF2. MAPK. MEKK1, NIK. Targets. IKK b. I k B. NF k B. LT = PA + LF ET = PA + EF. TRAF6. TAK1. MKK3,6. EF. LF. p38. Zinc metalloprotease. Targets. TRAF2. Pro-inflammatory caspases 1 ,11. FasL. TNF. Death-receptor Mediated

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ANTHRAX

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  1. ANTHRAX

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

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

  4. 2 1 Mechanisms of TIII secretion-induced cytotoxicity: Shigella, Salmonella, and Yersinia CD14 LPS Shigella TLR4 Yersinia Inflammation PMN’s IpaB Caspase 8 IKK (SipB-S.t.) IL-18 IL-1b Caspase 1 NF-kB Survival signals Inflammatory cyt. prod. Apoptosis Cell Death “Pyroptosis” Inflammatory apoptosis macrophage or macrophage-like cell

  5. 2 1 Immunologically silent Mechanisms of TIII secretion-induced cytotoxicity: Shigella, Salmonella, and Yersinia CD14 LPS Shigella TLR4 Yersinia Inflammation PMN’s IpaB Caspase 8 YopJ IKK (SipB-S.t.) IL-18 IL-1b Caspase 1 NF-kB Survival signals Inflammatory cyt. prod. Apoptosis Cell Death “Pyroptosis” Inflammatory apoptosis macrophage or macrophage-like cell

  6. NECROSIS vs. APOPTOSIS LPS, Hoechst (necrosis + apoptosis) LPS, TUNEL (apoptosis) No LPS, Hoechst No LPS, TUNEL 2 3 4 1

  7. Hoechst Annexin V DIC

  8. LPS

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