Overwhelming fungal infection in a Toll deficient background

Overwhelming fungal infection in a Toll Overwhelming fungal infection in a Toll deficient backgrounddeficient background

Comparison of structures of CD14, Toll and IL-1R

IL-1RIL-1R

TIRTIRdomaindomain

Ig-like Ig-like domainsdomainsCD14CD14

Leucine Leucine rich rich domainsdomains

GPI anchorGPI anchor CellCellmembranemembrane

NF-NF-BB

TollToll

TIRTIRdomaindomain

Leucine Leucine rich rich domainsdomains

NF-NF-BB

Nature, Vol 388, 24 july 1997, 394-397Nature, Vol 388, 24 july 1997, 394-397

Bruce BeutlerBruce Beutler

1

PG, LPLP

2 3 4 5 6 7 8 9 10

dsRNALPS

Flagellin

Zym, LP

ssRNA IMQ IMQ CpG

Toll-like receptors

Complexe ternaire :

1 homodimères + ARNdb

Permet le chevauchement des TIR engageant la signalisation.

Modèle proposéModèle proposé

Parallels between IL-1 and Spz functions

TollToll

MicrobialMicrobial inducersinducers

MammalsMammalsNF-NF-BB

IL-1RIL-1R

DefensinDefensin

IL-1IL-1

IL-1IL-1NF-NF-BB

TLRTLR

ProSpzProSpz

SpaetzleSpaetzle

DrosophilaDrosophila

NF-NF-BB

DrosomycinDrosomycin

PGRP-SAPGRP-SA GNBP-1GNBP-1

Sang

Mannose Rec. (MR, Endo180, DEC205, PLA2R)C-typeLectins

Others(LRR, CARD,…)

Ig-SF

TLR

h LIR (ILT)m PIR

NCRTREMhKIR

NKRP-1

mLY49

NKG2D

DC-SIGN receptorsDectin-2 (NCCL)Langerin

BDCA-2 (DLEC)

NOD moleculesTLR