Dual Activation of the Drosophila Toll Pathway by Two Pattern Recognition Receptors

Abstract

The Toll-dependent defense against Gram-positive bacterial infections in Drosophila is mediated through the peptidoglycan recognition protein SA (PGRP-SA). A mutation termed osiris disrupts the Gram-negative binding protein 1 (GNBP1) gene and leads to compromised survival of mutant flies after Gram-positive infections, but not after fungal or Gram-negative bacterial challenge. Our results demonstrate that GNBP1 and PGRP-SA can jointly activate the Toll pathway. The potential for a combination of distinct proteins to mediate detection of infectious nonself in the fly will refine the concept of pattern recognition in insects.

Molecular cloning and functional characterization of peptidoglycan recognition protein 6 in grass carp Ctenopharyngodon idella

“…Insect PGRPs have been shown to play an important role in detecting pathogens and activating NF-jB through the Toll and Imd pathways (Takehana et al, 2002;Gobert et al, 2003;Silverman et al, 2009). In vertebrates, PRRs such as TLRs and NODs were shown to participate in the signaling pathway leading to NF-jB activation (Shi et al, 2008;Hasegawa et al, 2008), whereas the link between PGRPs and NF-jB is still ambiguous.…”

“…Insect PGRPs are expressed mainly in immune competent sites such as fat body, gut and haemocytes (Werner et al, 2000). The activation of insect PGRPs by Gram-positive or Gram-negative bacteria may trigger Toll (Gobert et al, 2003) and immune deficiency (Imd) signal transduction pathways (Takehana et al, 2002) and the prophenol-oxidase cascade (Takehana et al, 2002), which results in the production of antimicrobial effectors. In addition, some insect PGRPs such as Drosophila PGRP-SC1 and PGRP-LB are N-acetylmuramoyl-L-alanine amidases (Kim et al, 2003;Mellroth et al, 2003), which can hydrolyze proinflammatory peptidoglycans.…”

The road to Toll

“…In contrast to the rapid identification of TLRs and their ligands, the Drosophila molecules involved in microbial recognition remained unknown until recently. At present, we know that some aspects of microbial recognition in flies are mediated by peptidoglycan-recognition proteins (PGRPs) and Gram-negative-bacteria-binding proteins (GNBPs) 43,[56][57][58][59][60] -two protein families identified, initially in other insects, by their capacity to bind microbial components [61][62][63][64] (FIG. 3).…”

Correlation of Differential Expression of Silkworm Antimicrobial Peptide Genes with Different Amounts of Rel Family Proteins and Their Gene Transcriptional Activity

“…15,16) Recently, lysine-containing peptidoglycans (Lys-type PGNs), a cell wall component of many Gram-positive bacteria, have been shown to elicit the Toll pathway through the PGN recognition protein PGRP-SA, and through the Gram-negative binding protein GNBP-1. 17,18) In contrast, meso-diaminopimelic acid-containing PGNs (DAP-type PGNs) from Gram-negative bacteria and a subclass of Gram-positive bacteria, which includes Bacillus species, have been reported to stimulate the IMD pathway through PGN recognition proteins, PGRP-LC and PGRP-LE. 19) Extracellular factors involved in the Toll pathway, such as Necrotic and Persephone, 20,21) and intercellular factors for the Toll and IMD pathways, have also been identified, 4,5) although further study is needed to understand these pathways further.…”