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Figure 1

Nature Immunology 7, 675 - 679 (2006)

TOLLing away in Brazil

Jane A Mitchell, Katherine A Fitzgerald, Anthony Coyle, Neal Silverman & Neil Cartwright

Fig 1 full size
Figure 1. Recognition and signaling in D. melanogaster.
Two pathways, Toll and Imd, respond to bacterial and fungal pathogens and activate NF-kappaB homologs (Dif, dorsal and Relish), driving antimicrobial peptide gene expression. D. melanogaster Toll is activated by the cytokine spätzle (spz). Pro-spätzle is found in the circulation and is cleaved after infection by the C-terminal proteinase domain protease spätzle processing enzyme (SPE). Alternative pathways respond to different pathogens and activate different C-terminal proteinase domain proteases (herrade, bereswinde and persephone), which all converge on the spätzle processing enzyme to activate Toll. Gram-positive bacteria, with lysine-containing peptidoglycan (LYS-PGN), are recognized by the soluble receptors PGRP-SA and/or PGRP-SD. Gram-negative bacteria produce diaminopimelic acid–type peptidoglycan (DAP-PGN), which is recognized by either PGRP-LC on the cell surface or by PGRP-LE inside the cell. Both of these receptors rely on a RHIM-like (receptor-interacting protein kinase homotypic interaction motif–like) motif for signal transduction (red bar). The Imd pathway induces the expression of PGRP-LB, which is a catalytic PGRP that degrades peptidoglycan. PGRP-LB and PGRP-SC1/2 function in the serum and gut to degrade peptidoglycan and thereby dampen the immune response. The response to the picorna-like drosophila C virus (DCV) is independent of these pathways. Instead, virus infection activates an unidentified signaling pathway that leads to production of antiviral factors in the infected cells as well as in neighboring cells via a putative interferon-like (IFN-like) factor and Janus kinase–signal transducer and activator of transcription (Jak-STAT) signaling. RNA interference (RNAi) is another highly conserved antiviral mechanism that is often inhibited by viral products, including the B2 protein from Flock House virus (FHV). dMyD88, drosophila MyD88.

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