Toll and IMD Pathways Synergistically Activate an Innate Immune Response in Drosophila melanogaster

Abstract

The inducible expression of antimicrobial peptide genes in Drosophila melanogaster is regulated by the conserved Toll and peptidoglycan recognition protein LC/immune deficiency (PGRP-LC/IMD) signaling pathways. It has been proposed that the two pathways have independent functions and mediate the specificity of innate immune responses towards different microorganisms. Scattered evidence also suggests that some antimicrobial target genes can be activated by both Toll and IMD, albeit to different extents. This dual activation can be mediated by independent stimulation or by cross-regulation of the two pathways. We show in this report that the Toll and IMD pathways can interact synergistically, demonstrating that cross-regulation occurs. The presence of Spätzle (the Toll ligand) and gram-negative peptidoglycan (the PGRP-LC ligand) together caused synergistic activation of representative target genes of the two pathways, including Drosomycin, Diptericin, and AttacinA. Constitutive activation of Toll and PGRP-LC/IMD could mimic the synergistic stimulation. RNA interference assays and promoter analyses demonstrate that cooperation of different NF-B-related transcription factors mediates the synergy. These results illustrate how specific ligand binding by separate upstream pattern recognition receptors can be translated into a broad-spectrum host response, a hallmark of innate immunity.

Wolbachiauses a host microRNA to regulate transcripts of a methyltransferase, contributing to dengue virus inhibition inAedes aegypti

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

“…The proliferation index is the ratio of the number of live intracellular bacteria at 6 h relative to the number of entered bacteria. to mammalian NF-jB and induction of antimicrobial peptides (Tanji et al, 2007). In mammals, porcine PGRPs are involved in antimicrobial peptide expression (Sang et al, 2005), and human PGRPs were reported to kill both Gram-positive and Gram-negative bacteria by synergistic effects with antibacterial peptides (Cho et al, 2005;Wang et al, 2007).…”

Lepidopteran species have a variety of defence strategies against bacterial infections

“…CecropinA, which is synergistically affected by the Imd and Toll pathways (Tanji et al 2007), was highly upregulated in G. mellonella and downregulated in A.…”