Drosophila as a Model to Study Brain Innate Immunity in Health and Disease

Lye, Shu Hui; Chtarbanova, Stanislava

doi:10.3390/ijms19123922

Cited by 26 publications

(27 citation statements)

References 132 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The finding that mostly sORFs, and among them many predicted AMPs are differentially expressed points to the immune system for being dysregulated by neonicotinoids. The best-characterized AMPs are expressed in the fat body upon pathogen exposure, but it is now recognized that glial cells in the brain also exert immune functions and express AMPs 37, 39,40 . Accordingly, the sORFs that we found to be differentially expressed upon chronic low dose thiamethoxam exposure might form a basal immune defence, similar to the antimicrobial environment present in saliva in vertebrates which many AMPs.…”

Section: Discussionmentioning

confidence: 99%

“…The Immune deficiency (Imd) pathway leads to expression of a different set of AMPs via the NFkappa-B transcription factor relish in response to peptidoglycans from primarily Gram-negative bacterial through the activation of pattern recognition receptors and a complex intracellular signalling cascade 29,30,35 . In addition to the fatbody, AMP expression activated by the Imd pathway has also been detected in glial cells in the brain [37][38][39][40] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thiamethoxam exposure deregulates short ORF gene expression in the honey bee and compromises immune response to bacteria

Décio

Ustaoglu

Derecka

et al. 2019

Preprint

View full text Add to dashboard Cite

Running title: Long-term low dose Thiamethoxam exposure induces short ORFs AbstractMaximizing crop yields heavily relies on the use of agrochemicals to control insect pests. One of the most widely used insecticides are neonicotinoids. Here, we analysed the impact of sub-lethal chronic long-term exposure to the neonicotinoid Thiamethoxam on gene expression and alternative splicing in brains of Africanized honey bees Apis mellifera. Our results reveal a small number of differentially regulated genes showing a concentration dependent response to two low doses of chronic, 10-day Thiamethoxam exposure. Unexpectedly, most of these genes have no annotated function, but encode short Open Reading Frames (sORFs), a characteristic feature of anti-microbial peptides. Likewise, we find that Thiamethoxam exposure sensitizes bees to infection by non-pathogenic bacteria Bacillus badius and Ochrobactrum anthropi. Moreover, infection with estimated single Serratia marcescens kills bees arguing that Varroa mites may essentially contribute to colony collapse by penetrating the cuticle to spread this pathogen. Our results implicate an altered immune response to Thiamethoxam exposure compromising the immune response leading to a decline in bee populations.Understanding the risk for honey bees requires detailed knowledge of cellular and molecular effects that result from the exposure to an insecticide in order to mitigate negative effects or refine the target specificity towards pest species.Changes in gene expression and processing of RNAs, including alternative splicing, are one of the options available to an organism to respond to environmental perturbations 15,16 . Sub-lethal exposure of xenobiotics can induce modulation of splicing reactions [17][18][19] .Neonicotinoid exposure has been linked to a decline in bee health including a reduction of immune competence 20 ;; 21-23 . Insects do not have antibodies and rely on the innate immune system to fight microbial infections. The best insight on insect immunity stems from studies in the fruit fly Drosophila melanogaster, where cellular and humoral immune responses have been identified 24,25 . The cellular response is mediated by three types of hematopoetic cell lineages 24,26,27 , while the humoral immune system can be split into Toll and Imd pathways [reviewed in 28 ]. The Tollpathway is triggered following an immune challenge by Gram-positive bacteria and fungi, ultimately leading to expression of antimicrobial peptides (AMPs) that are then secreted from the fat body into the hemolymph 24,29,30 . In contrast, the Immune deficiency (Imd) pathway leads to expression of a different set of AMPs after a Gramnegative bacterial infection activates pattern recognition receptors and a complex intracellular signaling cascade 24,25,29 . AMPs are short peptides of 10-100 amino acids and are characterised by an evolutionary dynamism among insect species 31 .We have previously shown that worker-bee larvae in colonies contaminated with the neonicotinoid imidacloprid, have altered expression o...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thiamethoxam exposure deregulates short ORF gene expression in the honey bee and compromises immune response to bacteria

Décio

Ustaoglu

Derecka

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Interestingly, transgenic flies overexpressing the protein develop LB-like inclusions, DA neuron degeneration and locomotor defects [56]. Furthermore, Drosophila shares high homology with the mammalian innate immune response of the brain, allowing the investigation of the PD-related neuroinflammatory mechanisms [57]. Therefore, considering these findings, the fruit fly represents a valuable system to model PD-linked genes and to dissect the related mechanisms of neurodegeneration.…”

Section: Melanogaster As a Model To Investigate Pd Pathologymentioning

confidence: 99%

Antioxidant Therapy in Parkinson’s Disease: Insights from Drosophila melanogaster

et al. 2020

View full text Add to dashboard Cite

Reactive oxygen species (ROS) play an important role as endogenous mediators in several cellular signalling pathways. However, at high concentrations they can also exert deleterious effects by reacting with many macromolecules including DNA, proteins and lipids. The precise balance between ROS production and their removal via numerous enzymatic and nonenzymatic molecules is of fundamental importance for cell survival. Accordingly, many neurodegenerative disorders, including Parkinson’s disease (PD), are associated with excessive levels of ROS, which induce oxidative damage. With the aim of coping with the progression of PD, antioxidant compounds are currently receiving increasing attention as potential co-adjuvant molecules in the treatment of these diseases, and many studies have been performed to evaluate the purported protective effects of several antioxidant molecules. In the present review, we present and discuss the relevance of the use of Drosophila melanogaster as an animal model with which to evaluate the therapeutic potential of natural and synthetic antioxidants. The conservation of most of the PD-related genes between humans and D. melanogaster, along with the animal’s rapid life cycle and the versatility of genetic tools, makes fruit flies an ideal experimental system for rapid screening of antioxidant-based treatments.

show abstract

“…Over the past few decades, many studies have been conducted in Drosophila melanogaster to gain insight into the pathophysiological processes underpinning AD, identify potentially important genes and biomarkers, and screen new drug candidates. Besides the wellknown advantages of using Drosophila as a model species [8], the host defense of the fruit fly rests entirely within its complex innate immune system, which makes it a desirable model for research on innate immunity in AD [9].…”

Section: Introductionmentioning

confidence: 99%

Dysregulation of antimicrobial peptide expression distinguishes Alzheimer’s disease from normal aging

Wang

Peng²,

et al. 2020

Aging

View full text Add to dashboard Cite

Alzheimer's disease (AD) is an age-related neurodegenerative disease with unknown mechanism that is characterized by the aggregation of abnormal proteins and dysfunction of immune responses. In this study, an integrative approach employing in silico analysis and wet-lab experiment was conducted to estimate the degrees of innate immune system relevant gene expression, neurotoxic Aβ42 generation and neuronal apoptosis in normal Drosophila melanogaster and a transgenic model of AD. Results demonstrated mRNA levels of antimicrobial peptide (AMP) genes gradually increased with age in wild-type flies, while which exhibited a trend for an initial decrease followed by subsequent increase during aging in the AD group. Time series and correlation analysis illustrated indicated a potential relationship between variation in AMP expression and Aβ42 concentration. In conclusion, our study provides evidence for abnormal gene expression of AMPs in AD flies with age, which is distinct from the expression profiles in the normal aging process. Aberrant AMP expression may participate in the onset and development of AD by inducing or accelerating Aβ deposition. These findings suggest that AMPs may serve as potential diagnostic biomarkers and therapeutic targets. However, further studies are required to elucidate the pathological effects and underlying mechanisms of AMP dysregulation in AD progression. GEO accession Sample Age Age group GSE122470 GSM3466957,

show abstract

Drosophila as a Model to Study Brain Innate Immunity in Health and Disease

Cited by 26 publications

References 132 publications

Thiamethoxam exposure deregulates short ORF gene expression in the honey bee and compromises immune response to bacteria

Thiamethoxam exposure deregulates short ORF gene expression in the honey bee and compromises immune response to bacteria

Antioxidant Therapy in Parkinson’s Disease: Insights from Drosophila melanogaster

Dysregulation of antimicrobial peptide expression distinguishes Alzheimer’s disease from normal aging

Contact Info

Product

Resources

About