Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: July 7, 2022

The innate immune response provides the first line of defense against invading pathogens, and disorders cause a variety diseases. fruit fly Drosophila melanogaster employs multiple reactions to resist infection. First, epithelial tissues function as physical barriers prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, lamellocytes encapsulate large particles, such wasp eggs, that cannot be phagocytosed. Regarding humoral responses, fat body, equivalent mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria fungi. has been shown powerful in vivo model for studying mechanism immunity host-pathogen interactions because higher organisms share conserved signaling pathways factors. Moreover, ease with which genetic physiological characteristics can manipulated prevents interference by adaptive immunity. this review, we discuss activated immunity, namely, Toll, Imd, JNK, JAK/STAT pathways, other factors, well relevant regulatory networks. We also review mechanisms different tissues, including hemocytes, lymph gland, muscles, gut brain coordinate responses. Furthermore, latest studies field are outlined review. summary, understanding underlying orchestration will help us better study human immunity-related

Language: Английский

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Macrophage acetyl-CoA carboxylase regulates acute inflammation through control of glucose and lipid metabolism

Science Advances, Journal Year: 2022, Volume and Issue: 8(47)

Published: Nov. 23, 2022

Acetyl-CoA carboxylase (ACC) regulates lipid synthesis; however, its role in inflammatory regulation macrophages remains unclear. We generated mice that are deficient both ACC isoforms myeloid cells. deficiency altered the lipidomic, transcriptomic, and bioenergetic profile of bone marrow–derived macrophages, resulting a blunted response to proinflammatory stimulation. In lipopolysaccharide (LPS), is required for early metabolic switch glycolysis remodeling macrophage lipidome. also resulted impaired innate immune functions, including bacterial clearance. Myeloid-specific deletion or pharmacological inhibition attenuated LPS-induced expression cytokines interleukin-6 (IL-6) IL-1β, while increased susceptibility peritonitis wild-type mice. Together, we identify critical thus clinically relevant, unexpected consequence inhibition.

Language: Английский

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Lipids as a key element of insect defense systems

Frontiers in Genetics, Journal Year: 2023, Volume and Issue: 14

Published: June 9, 2023

The relationship between insect pathogenic fungi and their hosts is a classic example of co-evolutionary arms race pathogen target host: parasites evolve towards mechanisms that increase advantage over the host, host increasingly strengthens its defenses. present review summarizes literature data describing direct indirect role lipids as an important defense mechanism during fungal infection. Insect comprise anatomical physiological barriers, cellular humoral response mechanisms. entomopathogenic have unique ability to digest cuticle by producing hydrolytic enzymes with chitin-, lipo- proteolytic activity; besides oral tract, pays way for entry within host. key factor in resistance infection presence certain types (free fatty acids, waxes or hydrocarbons) which can promote inhibit attachment cuticle, might also antifungal activity. Lipids are considered source energy, triglycerides stored fat body, structure analogous liver adipose tissue vertebrates. In addition, body plays innate immunity range bactericidal proteins polypeptides, one lysozyme. Energy derived from lipid metabolism used hemocytes migrate site infection, phagocytosis, nodulation encapsulation. One polyunsaturated acid, arachidonic synthesis eicosanoids, play several crucial roles physiology immunology. Apolipoprotein III compound activity, modulate signal molecule.

Language: Английский

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The circular RNA circbabo(5,6,7,8S) regulates lipid metabolism and neuronal integrity via TGF-β/ROS/JNK/SREBP signaling axis in Drosophila

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: March 5, 2025

Lipid droplets (LDs) are dynamic cytoplasmic lipid-storing organelles that play a pivotal role in maintaining cellular energy balance, lipid homeostasis, and metabolic signaling. Dysregulation of metabolism, particularly excessive lipogenesis, contributes to the abnormal accumulation LDs nervous system, which is associated with several neurodegenerative diseases. Circular RNAs (circRNAs) new class non-coding regulatory widely expressed eukaryotes. However, only subset has been functionally characterized. Here, we identified characterized circular RNA circbabo(5,6,7,8S) regulates lipogenesis neuronal integrity Drosophila melanogaster. derived from babo locus encodes type I receptor for transforming growth factor β (TGF-β). Depletion flies causes elevated droplet accumulation, progressive photoreceptor cell loss shortened lifespan, phenotypes rescued by restoring expression. In addition, RNA-seq epistasis analyses reveal these abnormalities caused aberrant activation SREBP signaling pathway. Furthermore, circbabo(5,6,7,8S)-depleted tissues display enhanced TGF-β pathway compromised mitochondrial function, resulting upregulation reactive oxygen species (ROS). Moreover, provide evidence protein circbabo(5,6,7,8S)-p, inhibits interfering assembly babo/put heterodimer complex. Lastly, show dysregulation ROS/JNK/SREBP cascade responsible LD neurodegeneration, lifespan elicited depletion. Our study demonstrates physiological protein-coding circRNA regulating metabolism integrity.

Language: Английский

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Origin and Development of the Adipose Tissue, a Key Organ in Physiology and Disease

Frontiers in Cell and Developmental Biology, Journal Year: 2021, Volume and Issue: 9

Published: Dec. 21, 2021

Adipose tissue is a dynamic organ, well known for its function in energy storage and mobilization according to nutrient availability body needs, charge of keeping the energetic balance organism. During last decades, adipose has emerged as largest endocrine organ human body, being able secrete hormones inflammatory molecules having an important impact multiple processes such adipogenesis, metabolism chronic inflammation. However, cellular progenitors, development, homeostasis different types are not fully known. decade, Drosophila melanogaster demonstrated be excellent model tackle some open questions field development endocrine/metabolic organs. Discoveries ranged from new regulating obesity subcellular mechanisms that regulate lipogenesis lipolysis. Here, we review available evidences on functions identify gaps future research. This may help understand molecular mechanism underlying pathophysiology this fascinating key tissue, contributing establish therapeutic target.

Language: Английский

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Reassessment of Pioglitazone for Alzheimer’s Disease

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: June 16, 2021

Alzheimer's disease is a quintessential 'unmet medical need', accounting for ∼65% of progressive cognitive impairment among the elderly, and 700,000 deaths in United States 2020. In 2019, cost caring sufferers was $244B, not including emotional physical toll on caregivers. spite this dismal reality, no treatments are available that reduce risk developing AD or offer prolonged mitiagation its most devestating symptoms. This review summarizes key aspects biology genetics disease, we describe how pioglitazone improves many patholophysiological determinants AD. We also summarize results pre-clinical experiments, longitudinal observational studies, clinical trials. The animal testing suggest can be corrective as well protective, efficacy enhanced time- dose-dependent manner, but dose-effect relations monotonic sigmoid. Longitudinal cohort studies suggests it delays onset dementia individuals with pre-existing type 2 diabetes mellitus, which small scale, unblinded pilot seem to confirm. However, placebo-controlled, blinded trials have borne out, discuss possible explanations these discrepancies.

Language: Английский

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DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(10)

Published: April 12, 2022

Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether is a cause or consequence of such state changes. The signalling pathways that integrate to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated deferiprone, therapeutic iron chelator stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling lipid metabolism within minutes treatment. DGAT1-dependent droplet biosynthesis occurred several hours before mitochondrial clearance, droplets bordering upon chelation. demonstrate DGAT1 inhibition restricts in vitro, impaired homeostasis viability. Importantly, genetic vivo significantly neuronal locomotor function Drosophila. Our data define as potent signal rapidly reshapes establishes an unexpected synergy between safeguards integrity.

Language: Английский

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Regulating metabolism to shape immune function: Lessons from Drosophila

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 138, P. 128 - 141

Published: April 16, 2022

Language: Английский

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IMD-mediated innate immune priming increases Drosophila survival and reduces pathogen transmission

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(6), P. e1012308 - e1012308

Published: June 10, 2024

Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by same pathogen can ‘prime’ response, resulting improved survival upon reinfection. Here, we investigated mechanistic basis and epidemiological consequences of innate priming fruit fly Drosophila melanogaster when infected with gram-negative bacterial Providencia rettgeri . We find that response to P is a long-lasting sexually dimorphic response. further explore it has potential curtail transmission reducing shedding spread. The enhanced individuals previously exposed non-lethal inoculum coincided transient decrease loads, provide strong evidence effect requires IMD-responsive antimicrobial-peptide Diptericin-B fat body. Further, show while Diptericin B main effector clearance, not sufficient for priming, which regulation IMD peptidoglycan recognition proteins. This work underscores plasticity complexity invertebrate responses infection, providing novel experimental effects on population-level outcomes.

Language: Английский

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Mapping the functional form of the trade-off between infection resistance and reproductive fitness under dysregulated immune signaling

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1012049 - e1012049

Published: Feb. 26, 2024

Immune responses benefit organismal fitness by clearing parasites but also exact costs associated with immunopathology and energetic investment. Hosts manage these tightly regulating the induction of immune signaling to curtail excessive restore homeostasis. Despite theoretical importance turning off response mitigate costs, experimentally connecting variation in negative regulation remains a frontier evolutionary immunology. In this study, we used dose-response approach manipulate RNAi-mediated knockdown efficiency cactus (IκBα), central regulator Toll pathway signal transduction flour beetles (Tribolium castaneum). By titrating activity across four distinct levels, derived shape relationship between investment traits host fitness, including infection susceptibility, lifespan, fecundity, body mass, gut Cactus knock-down increased overall magnitude inducible delayed their resolution dsRNA dose-dependent manner, promoting survival resistance following bacterial infection. However, benefits were counterbalanced integrity. Our results allowed us move beyond qualitative identification trade-off actually derive its functional form. This paves way quantitatively compare evolution impact regulatory elements on life-history trade-offs filling crucial gap our conceptual models network maintenance natural systems.

Language: Английский

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