4. Human skin transplantation model model in SCID mice
1 cm x 1 cm
Before
After
CB17/SCID
6 week-old females
Before
After
5. Nm targets human endothelial cells
(immuno histochemistry)
Anti human CD31
Anti Nm
6. PilD
PilF PilT
E
Assembly Retraction
Outer
membrane
Inner
membrane
PilC PilQ
PilW
Assembly
PilM, N, O, P
Stabilization
PilC, G, H, I, J, K, W
Maturation
PilC, I, J, K, W
PilE! Minor pilins!
(PilX, PilV, ComP)!
Prepilin
Minor pilins!
assembly!
re!traction!
(PilT)!
emergence !on the!
(PilQ)!
Functional Tfp (PilE, PilX, PilV, ComP)!
(PilD, F, M, N, O, P)! (PilC, G, H, I, J, K, W)!
cell surface!
(Craig et al, Molecular Cell 2006)
7. Non piliated strains do not colonize human skin grafts and do
not induce thrombosis nor vascular damage
X 100
X 1000
100 µm
100 µm
100 µm
10 µm
10 µm
10 µm
Nm antigen was only found within the cytoplasm of circulating or resident phagocytes
9. CD147 β2AR
Adhesion
PilE
PilV
PilE, PilV
Signalling
Type IV pilus Receptor :
Cellular Complex involving an « Adhesion Receptor » and a « Signalling Receptor »
Receptors for N. meningitidis Type IV pili
Coureuil et al, Cell, 2010
Bernard et al, Nature Medicine, 2014
10. ICAM-1
ICAM-2
CD44
E-selectin
Ezrin-Moesin
Coureuil et al, Science, 2009
Cdc42
Par3/PKCζ/Par6
complex
p120
β
α
Z0-1
Claudins
VE-Cadherin
permeability
Bacterial diffusion
Type IV pilus-mediated signaling events
Doulet et al, J Cell Biol, 2006
Lambotin et al J Cell Science, 2005
Eugene et al, J Cell Science, 2002
Hofffmann et al, J Cell Biol, 2001
11. How this meningococcal endothelial cells
interaction promotes the thrombotic leakage
syndrome responsible for Purpura fulminans ?
12. Two endothelial membranous receptors
are required for the activation of protein C
Coagulation triggers
(endotoxin, pro-inflammatory
cytokines)
Coagulation cascade
Fibrinogen Fibrin
(thrombus)
Endothelial cells
TM
Thrombin Thr Thr
PCaPC
EPCR
PC
-‐