Lack of an Antibacterial Response Defect in Drosophila Toll-9 Mutant

Karine Narbonne-Reveau,Bernard Charroux,Julien Royet,Andreas Bergmann

doi:10.1371/journal.pone.0017470

Karine Narbonne-Reveau, Bernard Charroux + Show 2 more

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https://doi.org/10.1371/journal.pone.0017470

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Abstract

Toll and Toll-like receptors represent families of receptors involved in mediating innate immunity response in insects and mammals. Although Drosophila proteome contains multiple Toll paralogs, Toll-1 is, so far, the only receptor to which an immune role has been attributed. In contrast, every single mammalian TLR is a key membrane receptor upstream of the vertebrate immune signaling cascades. The prevailing view is that TLR-mediated immunity is ancient. Structural analysis reveals that Drosophila Toll-9 is the most closely related to vertebrate TLRs and utilizes similar signaling components as Toll-1. This suggests that Toll-9 could be an ancestor of TLR-like receptors and could have immune function. Consistently, it has been reported that over-expression of Toll-9 in immune tissues is sufficient to induce the expression of some antimicrobial peptides in flies. These results have led to the idea that Toll-9 could be a constitutively active receptor that maintain significant levels of antimicrobial molecules and therefore provide constant basal protection against micro-organisms. To test theses hypotheses, we generated and analyzed phenotypes associated with a complete loss-of-function allele of Toll-9. Our results suggest that Toll-9 is neither required to maintain a basal anti-microbial response nor to mount an efficient immune response to bacterial infection.

Highlights

Innate immunity is a rapid and efficient response that multicellular organisms mount to defend themselves against infection and that has been conserved throughout evolution
The Toll pathway is triggered by Gram-positive bacteria with Lysine-type peptidoglycan (Lys-type PGN), fungi and yeast, and mediates phosphorylation and subsequent degradation of the IkB-like inhibitor Cactus, freeing the NF-kB transcription factor Dif that translocates into the nuclear compartment where it induces the expression of several genes encoding antimicrobial peptides (AMPs), including Drosomycin and Cecropin [9,10,11,12,13]
The findings that Toll-Like Receptor (TLR) are implicated in the immune response in mammals and that Toll participates in the Drosophila host response has led to the idea that TLR-mediated immunity is originating from ancestor of bilaterian

Summary

Introduction

Innate immunity is a rapid and efficient response that multicellular organisms mount to defend themselves against infection and that has been conserved throughout evolution (reviewed in [1,2]). Drosophila humoral immune response is under the transcriptional control of two NF-kB signaling cascades, the Immune deficiency (Imd) and the Toll pathways, which closely resemble mammalian TNF-R and Toll-Like Receptor (TLR), respectively (reviewed in [5,6]). The Imd pathway can be activated by Gram-negative bacteria that contain diaminopimelic acid type peptidoglycan (DAP-type PGN) in their cell wall. The Toll pathway is triggered by Gram-positive bacteria with Lysine-type peptidoglycan (Lys-type PGN), fungi and yeast, and mediates phosphorylation and subsequent degradation of the IkB-like inhibitor Cactus, freeing the NF-kB transcription factor Dif that translocates into the nuclear compartment where it induces the expression of several genes encoding AMPs, including Drosomycin and Cecropin [9,10,11,12,13]

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