Program in Molecular Medicine
Animals; Animals, Genetically Modified; Carrier Proteins; Cells, Cultured; Drosophila melanogaster; *Immunity, Natural; Male; Signal Transduction; Toll-Like Receptors
Life Sciences | Medicine and Health Sciences
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 Spatzle (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-kappaB-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.
DOI of Published Version
Mol Cell Biol. 2007 Jun;27(12):4578-88. Epub 2007 Apr 16. Link to article on publisher's site
Molecular and cellular biology
Tanji, Takahiro; Hu, Xiaodi; Weber, Alexander N. R.; and Ip, Y. Tony, "Toll and IMD pathways synergistically activate an innate immune response in Drosophila melanogaster" (2007). Open Access Articles. 1332.