Conventional and non-conventional Drosophila Toll signaling

Abstract

The discovery of Toll in Drosophila and of the remarkable conservation in pathway composition and organization catalyzed a transformation in our understanding of innate immune recognition and response. At the center of that picture is a cascade of interactions in which specific microbial cues activate Toll receptors, which then transmit signals driving transcription factor nuclear localization and activity. Experiments gave substance to the vision of pattern recognition receptors, linked phenomena in development, gene regulation, and immunity into a coherent whole, and revealed a rich set of variations for identifying non-self and responding effectively. More recently, research in Drosophila has illuminated the positive and negative regulation of Toll activation, the organization of signaling events at and beneath membranes, the sorting of information flow, and the existence of non-conventional signaling via Toll-related receptors. Here, we provide an overview of the Toll pathway of flies and highlight these ongoing realms of research.

Nitric Oxide Levels Regulate the Immune Response of Drosophila melanogaster Reference Laboratory Strains to Bacterial Infections

“…We examined the transcriptional levels of two AMP genes (Diptericin and Defensin) representative of Toll and Imd immune pathway activation in D. melanogaster (24,25). We chose to examine the transcriptional activation of those two AMP genes because diptericin is effective against Gramnegative bacteria and defensin is active against Gram-positive bacteria (26).…”

“…To estimate the bacterial load at various time points (0, 3,6,12,24, and 48 h) after bacterial infection, flies from each treatment were individually crushed and homogenized using an electronic pestle in 1.5-ml Eppendorf tubes containing 1 ml of LB medium. The numbers of bacteria (CFU) within each fly were estimated by serial dilution and plating on LB agar plates.…”

β-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity

“…In Drosophila, the Cactus, a homolog of IB in mammals, is the main cytoplasmic inhibitor of Dorsal (a homolog of mammalian NF-B) (12). The activation of the Toll pathway is also negatively regulated by serpins (13). Kurtz, a ␤-arrestin in Drosophila, negatively controls Toll signaling and systemic inflammation at the level of sumoylation (14).…”

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

“…To further investigate innate immune regulation of epidermal wound gene activation, we next focused on the analysis of Toll/NF-κB pathway proteins acting downstream of the Toll receptor. To determine their effect on ple-WE1 wound reporter, we wounded embryos homozygous mutant for null mutations in either tube or Myd88, both of which encode intracellular adaptor proteins (29). We also wounded embryos in mutants for dorsal (dl) and Dif, which encode NF-κB family transcription factors.…”