Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

Abdelsadik, Ahmed; Roeder, Thomas

doi:10.1186/1471-2164-11-265

Cited by 15 publications

(13 citation statements)

References 37 publications

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“…We propose that the premature release of the Dop1R2 inhibitory effect (using RNAi approaches) translates into increased expression of the L71 defensin-like polypeptides, as well as a series of antimicrobial peptides, stress proteins/chaperones, cuticle and morphogenesis proteins in a de-synchronized manner. This misexpression could be highly detrimental to the developing fly, in agreement with a number of studies discussed above [ 80 , 86 , 103 ].…”

Section: Discussionsupporting

confidence: 88%

“…Such deregulated activation of the immune system (in response to Dop1R2 knockdown) in the developing fly may contribute to the observed lethal phenotype. It is well-established that in Drosophila the balance between repression and induction of the immune defense is tightly regulated, and ensures optimal growth and size at metamorphosis [ 80 – 82 ]. Control of the innate immunity enables larval growth amidst the plethora of bacteria and fungi found in the natural larval feeding environment and ensures high tolerance for the larval gut commensal microbiota, which has been shown to promote development [ 83 – 85 ].…”

Section: Discussionmentioning

confidence: 99%

“…Conversely, deregulated immune responses can alter normal fly growth and development. Abdelsadik and Roeder (2010) have demonstrated that chronic activation of the immune system of larval salivary glands is detrimental to fly development and survival [ 80 ]. Similarly, Rynes et al (2012) have shown that chronic inflammation of the larval gut epithelium results in developmental delay, growth retardation and lethality [ 86 ].…”

Section: Discussionmentioning

confidence: 99%

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A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis

et al. 2016

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BackgroundInsect metamorphosis relies on temporal and spatial cues that are precisely controlled. Previous studies in Drosophila have shown that untimely activation of genes that are essential to metamorphosis results in growth defects, developmental delay and death. Multiple factors exist that safeguard these genes against dysregulated expression. The list of identified negative regulators that play such a role in Drosophila development continues to expand.ResultsBy using RNAi transgene-induced gene silencing coupled to spatio/temporal assessment, we have unraveled an important role for the Drosophila dopamine 1-like receptor, Dop1R2, in development. We show that Dop1R2 knockdown leads to pre-adult lethality. In adults that escape death, abnormal wing expansion and/or melanization defects occur. Furthermore we show that salivary gland expression of this GPCR during the late larval/prepupal stage is essential for the flies to survive through adulthood. In addition to RNAi-induced effects, treatment of larvae with the high affinity D1-like receptor antagonist flupenthixol, also results in developmental arrest, and in morphological defects comparable to those seen in Dop1R2 RNAi flies. To examine the basis for pupal lethality in Dop1R2 RNAi flies, we carried out transcriptome analysis. These studies revealed up-regulation of genes that respond to ecdysone, regulate morphogenesis and/or modulate defense/immunity.ConclusionTaken together our findings suggest a role for Dop1R2 in the repression of genes that coordinate metamorphosis. Premature release of this inhibition is not tolerated by the developing fly.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-016-0115-z) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis

et al. 2016

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“…1A), demonstrating that BBG was required for the normal lifespan of Drosophila. Because constitutive activation of the Drosophila immune response is known to reduce lifespan (9,14,17) the reduction in LT 50 noted above could reflect a stronger constitutive immune response. Analysis of the IMD pathway diptericin-LacZ reporter staining indeed revealed a much higher constitutive activation of the pathway in the anterior midgut of bbg B211/B211 flies than in WT flies (Fig.…”

Section: Bbg Promotes Immune Tolerance In the Gut And Is Required Formentioning

confidence: 99%

big bang gene modulates gut immune tolerance in Drosophila

Bonnay

Cohen-Berros

Hoffmann

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila . Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang ( bbg ) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

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“…The boundary between the midand hindgut corresponds to the branching point of the Malpighian tubules. These renal-like evaginations absorb solutes, water, and waste from the surrounding hemolymph (insect blood) and release them into the gut lumen in the form of solid nitrogenous compounds [4]. The rest of the gut consists of the hindgut, which resorbs water and ions and expels undigested waste.…”

Section: Drosophila Gut Architecture and Functionmentioning

confidence: 99%

Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster

Royet

2011

Cell. Mol. Life Sci.

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Insects mostly develop on decaying and contaminated organic matter and often serve as vectors of biologically transmitted diseases by transporting microorganisms to the plant and animal hosts. As such, insects are constantly ingesting microorganisms, a small fraction of which reach their epithelial surfaces, mainly their digestive tract, where they can establish relationships ranging from symbiosis to mutualism or even parasitism. Understanding the tight physical, genetic, and biochemical interactions that takes place between intestinal epithelia and either resident or infectious microbes has been a long-lasting objective of the immunologist. Research in this field has recently been re-vitalized with the development of deep sequencing techniques, which allow qualitative and quantitative characterization of gut microbiota. Interestingly, the recent identification of regenerative stem cells in the Drosophila gut together with the initial characterization of Drosophila gut microbiota have opened up new avenues of study aimed at understanding the mechanisms that regulate the dialog between the Drosophila gut epithelium and its microbiota of this insect model. The fact that some of the responses are conserved across species combined with the power of Drosophila genetics could make this organism model a useful tool to further elucidate some aspects of the interaction occurring between the microbiota and the human gut.

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Chronic activation of the epithelial immune system of the fruit fly's salivary glands has a negative effect on organismal growth and induces a peculiar set of target genes

Cited by 15 publications

References 37 publications

A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis

A critical role for the Drosophila dopamine D1-like receptor Dop1R2 at the onset of metamorphosis

big bang gene modulates gut immune tolerance in Drosophila

Epithelial homeostasis and the underlying molecular mechanisms in the gut of the insect model Drosophila melanogaster

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