Shigella Effectors at Work - EMBO

Shigella Effectors at Work - EMBO Shigella Effectors at Work - EMBO

14.07.2013 Views

LPS/LBP MD2/CD14 TLR4 (LRR) TIRAF TRAM TIRAP MyD88 TRAF6/2 MEK MAPK IRAK1 IRAK4 -P -P p38 JNK Erk1/2 Histone H3 tail S10 P K9 Met K14 Ac P38/Erk P38/Erk P P NF-κB MAPK-TFs RICK/RIP2 NF-κB Pol II II Card Card NBS IKK P NF-κB IκB SCF βTRCP IκB Ub UbUb S10 P K9 Met K14 Ac Nucleosome Heterochromatin Induction of innate immunity genes « inflammation » Nod2 Nod1 E2 Ub Ub (LRR) PGN (Muropeptides) Proteasomal degradation Nod1 apical staining in TC7 epithelial cells (confirmed confirmed in vivo) Kufer et al., Cell.Microbiol Cell Microbiol., ., 2008 Colocalization of Nod1 and IKKγ IKK (NEMO) Inflammatory mediators: mediators mediators: iNOS, iNOS iNOS, , Cox2 Adhesion molecules: molecules molecules: : VCAM, ICAM, E-Selectin E- E-Selectin Selectin Cytokines/chemokines Cytokines/ Cytokines/chemokines: chemokines: : IL-6, IL-8, TNFα, TNF TNFα, , MCP-1, MIP-1α, MIP-1 MIP-1α, , CCL20, ... Antimicrobial peptides and associated molecules Girardin et coll., EMBO Repts, 2001 Pédron dron et al., J.Biol J. Biol.Chem Chem., ., 2002 Girardin et coll.., Science, 2003 Girardin et coll., J.Biol.Chem., 2003

GlcNAc O O CH O HCCH 3 CO CO CH 3 L-Ala D-Glu MurNAc NH Meso-DAP DAP O Shigella Shigella ? LRR NBS/NACHT CARD RICK IKK MTP JNK Pro-inflammatory genes activated by NF-κB Nod1 Functions of Nod1 Caspase 9 Apoptosis Girardin et coll., EMBO Repts, 2001 Girardin et coll.., Science, 2003 Girardin et coll., J.Biol.Chem., 2004

LPS/LBP<br />

MD2/CD14<br />

TLR4<br />

(LRR)<br />

TIRAF<br />

TRAM<br />

TIRAP<br />

MyD88<br />

TRAF6/2<br />

MEK<br />

MAPK<br />

IRAK1<br />

IRAK4<br />

-P<br />

-P<br />

p38 JNK Erk1/2<br />

Histone H3 tail<br />

S10 P<br />

K9 Met<br />

K14 Ac<br />

P38/Erk P38/Erk<br />

P P<br />

NF-κB<br />

MAPK-TFs<br />

RICK/RIP2<br />

NF-κB<br />

Pol II II<br />

Card Card NBS<br />

IKK<br />

P<br />

NF-κB<br />

IκB<br />

SCF βTRCP<br />

IκB<br />

Ub<br />

UbUb<br />

S10 P<br />

K9 Met<br />

K14 Ac<br />

Nucleosome<br />

Heterochrom<strong>at</strong>in<br />

Induction of inn<strong>at</strong>e immunity genes<br />

« inflamm<strong>at</strong>ion »<br />

Nod2<br />

Nod1<br />

E2<br />

Ub<br />

Ub<br />

(LRR)<br />

PGN<br />

(Muropeptides)<br />

Proteasomal<br />

degrad<strong>at</strong>ion<br />

Nod1 apical staining in TC7 epithelial cells<br />

(confirmed confirmed in vivo)<br />

Kufer et al., Cell.Microbiol<br />

Cell Microbiol., ., 2008<br />

Colocaliz<strong>at</strong>ion of Nod1 and IKKγ IKK (NEMO)<br />

Inflamm<strong>at</strong>ory medi<strong>at</strong>ors: medi<strong>at</strong>ors medi<strong>at</strong>ors: iNOS, iNOS iNOS, , Cox2<br />

Adhesion molecules: molecules molecules: : VCAM, ICAM, E-Selectin E- E-Selectin Selectin<br />

Cytokines/chemokines<br />

Cytokines/ Cytokines/chemokines: chemokines: : IL-6, IL-8, TNFα, TNF TNFα, , MCP-1,<br />

MIP-1α, MIP-1 MIP-1α, , CCL20, ...<br />

Antimicrobial peptides and associ<strong>at</strong>ed molecules<br />

Girardin et coll., <strong>EMBO</strong> Repts, 2001<br />

Pédron dron et al., J.Biol J. Biol.Chem Chem., ., 2002<br />

Girardin et coll.., Science, 2003<br />

Girardin et coll., J.Biol.Chem., 2003

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