How is infection sensed in insects?
Fungi Yeast |
Gram positive |
Gram negative |
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bacteria |
bacteria |
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Spz |
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Toll |
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Toll-2? |
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IMD (RIP) |
Dif (NF- B ) |
Relish (NF- B ) |
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Drosomycin |
Diptericin |
The mutant semmelweis reveals |
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differences in the sensing of bacteria |
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and fungi |
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Streptococcus faecalis |
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Beauveria bassiana |
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100 |
(Gram +) |
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Survival rate (%) |
100 |
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(Fungus) |
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wt |
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wt |
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50 |
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50 |
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Survivalrate(%) |
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Seml |
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Seml |
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0 0 |
12 |
24 |
36 |
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0 0 |
1 |
2 |
3 |
4 |
5 |
6 |
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Time p.i. (h) |
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Time p.i. (d) |
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Michel et al Nature (20
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The PeptidoGlycan Recognition Protein |
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(PGRP) family (drosophila) |
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SA |
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Semmelweis |
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203 |
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SB1 |
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190 |
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SB2 |
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182 |
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SC1a |
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185 |
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SC1b |
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185 |
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SC2 |
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184 |
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SD |
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186 |
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LA |
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280 |
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LB |
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215 |
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LC |
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520 |
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LD |
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505 |
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LE |
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345 |
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LF |
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337 |
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Signal peptide |
PGRP domain with/without amidase |
Transmembrane domain |
activity |
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Sensing Gram-negative infections in Drosophila
Survival rate
infection by Enterobacter cloacae (Gram-)
100
PGRP-SA -/-
50
PGRP-LC -/-
12 |
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24 |
36 |
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48 |
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Time (h) |
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E. cloacae: - |
+ + + |
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Diptericin |
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- |
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wt |
wt SA -/-LC -/ |
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Gottar et al Nature (2
Peptidoglycan structure Lys-type
(most Gram+)
Glycan strand |
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GlcNAc |
MurNAc |
GlcNAc |
MurNAc |
GlcNAc |
MurNAc |
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L-Ala |
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L-Ala |
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L-Ala |
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D-Glu |
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D-Glu |
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D-Glu |
Short peptide L-Lys |
(Gly) D-Ala |
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L-Lys |
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bridge |
D-Ala |
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L-Lys |
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D-Ala |
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D-Glu |
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D-Glu |
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L-Ala |
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L-Ala |
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Glycan strand |
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MurNAc |
GlcNAc |
MurNAc |
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GlcNAc |
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Peptidoglycan structure
Glycan strand
GlcNAc |
MurNAc |
GlcNAc |
MurNAc |
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L-Ala |
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L-Ala |
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D- |
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Glu |
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D- |
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Glu |
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Short peptide DAP |
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(Gly) |
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D-Ala |
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bridge |
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D-Ala |
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DAP |
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D- |
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Glu |
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L-Ala |
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Glycan strand |
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MurNAc |
GlcNAc |
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GlcNAc |
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DAP-type
(Gram-)
TCT
GlcNAc MurNAc
L-Ala
D-Glu
DAP
D-Ala
D-Glu
L-Ala
MurNAc
TCT/PGRP-LC complex
DAP
From Chang et al (2006), Science 311: 17
Drosophila recognition proteins for microbial structures
Signal PGRP domain peptide
PGRP-SA |
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(semmelweis) |
PGN (Ly |
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180203 |
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27 38 |
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Michel et al (2001) Nat |
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Transmembrane |
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PGRP-LC |
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PGRP domain |
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domain |
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295 317 |
353 |
PGN (DA |
498 520 |
Gottar et al (2002) Nat
GNBP-1
GNBP-3
GNBP homology |
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-glucanase |
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domain |
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domain |
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PGN (Ly |
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19 |
117 |
194 |
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447 |
492 |
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GNBP homology |
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-glucanase |
Gobert et al (2003) Scie |
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domain |
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domain |
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- ,3 gluc |
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26 |
121 |
242 |
466 |
492 |
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Gottar et al (2006) C
Fungi Yeast |
Gram positive Gram negative |
Virus |
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bacteria |
bacteria |
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-glucansl |
PGRP-SD |
Lys-PGN |
DAP-PGN |
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PGRP-SA |
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Microbial |
GNBP-3 |
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protease |
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GNBP- |
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s |
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Spaetzle |
Toll |
PGRP-LC |
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MyD88 |
IMD (RIP) |
? |
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Relish (NF- B ) |
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Dif (NF- B ) |
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Drosomycin |
Diptericin |
? |
Ferrandon et al (2007) Nat Rev Im
988 |
IL- R is cloned. |
989 |
Charles Janeway proposes the concept of pattern-recognition |
990 |
receptors. |
CD14 and LPS-binding protein are identified as components of the |
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99 |
LPS receptor complex. |
Sequence similarity between Toll and IL-1R1 identified |
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993– 996 |
Pathogen-specific immune signalling found to involve induction of |
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antimicrobial peptides by members of the NF-κB family in Drosophila |
994 |
melanogaster. |
Plant protein N is shown to be involved in disease resistance and to |
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996 |
have a TIR domain that is similar to Toll and IL-1R1. |
The Toll pathway is shown to regulate the antifungal response in D. |
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997 |
melanogaster. |
The first human homologue of Toll receptor is cloned (hToll; later |
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renamed TLR4). |
998 |
A role for MYD88 in IL-1 receptor signalling is identified. |
Four further human TLRs are identified. |
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999 |
TLR4 is identified as the signalling receptor for LPS. |
LPS signalling is found to require MYD88. |
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The requirement of MD2 for TLR4 responsiveness to LPS is identified. |
2000-2002 |
Ligands for TLR2- heterodimeric complexes are identified |
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Viral antagonists of TLRs are identified. |
200 |
TLR9 is characterized as the receptor for CpG-DNA. |
The first TLR that recognizes viral components is identified (TLR3). |
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Flagellin is identified as a ligand for TLR5. |
2002 |
MAL (also known as TIRAP) is discovered. |
TRIF is discovered. |
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2002-2009 |
Endogenous ligands for TLRs are identified. |
2003 |
TRAM is discovered. |
2004 |
TLR7 and TLR8 are reported to recognize viral ssRNA. |
2006 |
The first function for mammalian SARM1 (a regulator of TRIF) is |
2007-2009 |
reported. |
Structures of several TLR–ligand complexes (including TLR4, TLR2– |
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TLR1, TLR2–TLR6 and TLR3) are solved. |