Drosophila melanogaster insect innate immunity

Immune systems are of pivotal importance to any living organism on Earth, as they protect the organism against deleterious effects of viral infections. Though the current knowledge about these systems is still biased towards the immune response in vertebrates, some studies have focused on the identification and characterization of components of invertebrate antiviral immune systems. Two classic model organisms, the insect Drosophila melanogaster and the nematode Caenorhabditis elegans, were instrumental in the discovery of several important components of the innate immune system, such as the Toll-like receptors and the RNA interference pathway...

Acetylcholine (ACh) is one the major neurotransmitters in insects, whose role in mediating synaptic interactions between neurons in the central nervous system is well characterized. It also plays largely unexplored regulatory functions in non-neuronal tissues. Here we demonstrate that ACh signaling is involved in the modulation of the innate immune response of Drosophila melanogaster. Knockdown of ACh synthesis or ACh vesicular transport in neurons reduced the activation of drosomycin (drs), a gene encoding an antimicrobial peptide, in adult flies infected with a Gram-positive bacterium...

The melanization and Toll pathways, regulated by a network of serine proteases and noncatalytic serine protease homologs (SPHs), have been investigated mostly in adult and larval insects. However, how these innate immune reactions are regulated in insect eggs remains unclear. Here we present evidence from transcriptome and proteome analyses that extra-embryonic tissues (yolk and serosa) of early-stage Manduca sexta eggs are immune competent, with expression of immune effector genes including prophenoloxidase and antimicrobial peptides...

Thioester-containing proteins (TEPs) are present in many animal species ranging from deuterostomes to protostomes, which emphasizes their evolutionary conservation and importance in animal physiology. Phylogenetically, insect TEPs share sequence similarity with mammalian α2-macroglobulin. Drosophila melanogaster is specifically considered a superb model for teasing apart innate immune processes. Here we review recent discoveries on the involvement of Drosophila TEPs in the immune response against bacterial pathogens, nematode parasites, and parasitoid wasps...

Metazoans have developed strategies to protect themselves from pathogenic attack. These preserved mechanisms constitute the immune system, composed of innate and adaptive responses. Among the two kinds, the innate immune system involves the activation of a fast response. NF-κB signaling pathways are activated during infections and lead to the expression of timely-controlled immune response genes. However, activation of NF-κB pathways can be deleterious when uncontrolled. Their regulation is necessary to prevent the development of inflammatory diseases or cancers...

BACKGROUND: Rhodnius prolixus is an important vector of Trypanosoma cruzi, the causal agent of Chagas disease in humans. Despite the medical importance of this and other triatomine vectors, the study of their immune responses has been limited to a few molecular pathways and processes. Insect immunity studies were first described for holometabolous insects such as Drosophila melanogaster, and it was assumed that their immune responses were conserved in all insects. However, study of the immune responses of triatomines and other hemimetabolous insects has revealed discrepancies between these and the Drosophila model...

In many species, female reproductive investment comes at a cost to immunity and resistance to infection. Mated Drosophila melanogaster females are more susceptible to bacterial infection than unmated females. Transfer of the male seminal fluid protein Sex Peptide reduces female post-mating immune defense. Sex Peptide is known to cause both short- and long-term changes to female physiology and behavior. While previous studies showed that females were less resistant to bacterial infection as soon as 2.5 h and as long as 26...

Organisms are commonly infected by a diverse array of pathogens and mount functionally distinct responses to each of these varied immune challenges. Host immune responses are characterized by the induction of gene expression, however, the extent to which expression changes are shared among responses to distinct pathogens is largely unknown. To examine this, we performed meta-analysis of gene expression data collected from Drosophila melanogaster following infection with a wide array of pathogens. We identified 62 genes that are significantly induced by infection...

The antiviral role of innate immune responses mediated by the NF-κB family of transcription factors is well established in vertebrates but was for a long time less clear in insects. Insects encode two canonical NF-κB pathways, the Toll and Imd ('immunodeficiency') pathways, which are best characterised for their role in antibacterial and antifungal defence. An increasing body of evidence has also implicated NF-κB-mediated innate immunity in antiviral responses against some, but not all, viruses. Specific pattern recognition receptors (PRRs) and molecular events leading to NF-κB activation by viral pathogen-associated molecular patterns (PAMPs) have been elucidated for a number of viruses and insect species...

Immune priming describes the phenomenon whereby after a primary pathogen exposure, a host more effectively fights a lethal secondary exposure (challenge) to the same pathogen. Conflicting evidence exists for immune priming in invertebrates, potentially due to heterogeneity across studies in the pathogen species tested, the antigen preparation for the primary exposure, and the phenotypic trait used to test for priming. To explore these factors, we injected Drosophila melanogaster with one of two bacterial species, Lactococcus lactis or Providencia burhodogranariea , which had either been heat-killed or inactivated with formaldehyde, or we injected a 1:1 mixture of the two inactivation methods...

Insects occupy a central position in the biosphere. They are able to resist infections even though they lack an adaptive immune system. Drosophila melanogaster has been used as a potent genetic model to understand innate immunity both in invertebrates and vertebrates. Its immune system includes both humoral and cellular arms. Here, we review how the distinct immune responses are triggered upon sensing infections, with an emphasis on the mechanisms that lead to systemic humoral immune responses. As in plants, the components of the cell wall of microorganisms are detected by dedicated receptors...

Insect metamorphosis is triggered by the production, secretion and degradation of 20-hydroxyecdysone (ecdysone). In addition to its role in developmental regulation, increasing evidence suggests that ecdysone is involved in innate immunity processes, such as phagocytosis and the induction of antimicrobial peptide (AMP) production. AMP regulation includes systemic responses as well as local responses at surface epithelia that contact with the external environment. At pupariation, Drosophila melanogaster increases dramatically the expression of three AMP genes, drosomycin (drs), drosomycin-like 2 (drsl2) and drosomycin-like 5 (drsl5)...

Cecropins are small helical secreted peptides with antimicrobial activity that are widely distributed among insects. Genes encoding cecropins are strongly induced upon infection, pointing to their role in host-defense. In Drosophila, four cecropin genes clustered in the genome (CecA1, CecA2, CecB and CecC) are expressed upon infection downstream of the Toll and Imd pathways. In this study, we generated a short deletion ΔCecA-C removing the whole cecropin locus. Using the ΔCecA-C deficiency alone or in combination with other antimicrobial peptide (AMP) mutations, we addressed the function of cecropins in the systemic immune response...

Pyroptosis has been described in mammalian systems to be a form of programmed cell death that is important in immune function through the subsequent release of cytokines and immune effectors upon cell bursting. This form of cell death has been increasingly well-characterized in mammals and can occur using alternative routes however, across phyla, there has been little evidence for the existence of pyroptosis. Here we provide evidence for an ancient origin of pyroptosis in an in vivo immune scenario in Drosophila melanogaster...

Drosophila sechellia is a dietary specialist endemic to the Seychelles islands that has evolved to consume the fruit of Morinda citrifolia. When ripe, the fruit of M. citrifolia contains octanoic acid and hexanoic acid, two medium-chain fatty acid volatiles that deter and are toxic to generalist insects. Drosophila sechellia has evolved resistance to these volatiles allowing it to feed almost exclusively on this host plant. The genetic basis of octanoic acid resistance has been the focus of multiple recent studies, but the mechanisms that govern hexanoic acid resistance in D...

In adult mammals, blood cells are formed from hematopoietic stem progenitor cells, which are controlled by a complex cellular microenvironment called "niche". Drosophila melanogaster is a powerful model organism to decipher the mechanisms controlling hematopoiesis, due both to its limited number of blood cell lineages and to the conservation of genes and signaling pathways throughout bilaterian evolution. Insect blood cells or hemocytes are similar to the mammalian myeloid lineage that ensures innate immunity functions...

In mammals, plant lectinshave been shown to possess immunomodulatory properties, acting in both the innate and adaptive immune system to modulate the production of mediators of the immune response, ultimately improving host defences. At present, knowledge of immunomodulatory effects of plant lectins in insects is scarce. Treatment of insect cells with the Orysa sativa lectin, Orysata, was previously reported to induce cell aggregation, mimicking the immune process of encapsulation. In this project we investigated the potential immunomodulatory effects of this mannose-binding lectin using Drosophila melanogaster S2 cells...

Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger 2'3'-cGAMP and controls activation of innate immunity in mammalian cells1-5 . Animal genomes typically encode multiple proteins with predicted homology to cGAS6-10 , but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors capable of recognizing divergent molecular patterns and catalyzing synthesis of distinct nucleotide second messenger signals...

The Toll signaling pathway is highly conserved from insects to mammals. Drosophila is a model species that is commonly used to study innate immunity. Although many studies have assessed protein-coding genes that regulate the Toll pathway, it is unclear whether long noncoding RNAs (lncRNAs) play regulatory roles in the Toll pathway. Here, we evaluated the expression of the lncRNA CR46018 in Drosophila. Our results showed that this lncRNA was significantly overexpressed after infection of Drosophila with Micrococcus luteus...

Peptidoglycan recognition proteins (PGRPs) are ubiquitous among animals and play pivotal functions in insect immunity. Non-catalytic PGRPs are involved in the activation of immune pathways by binding to the peptidoglycan (PGN), whereas amidase PGRPs are capable of cleaving the PGN into non-immunogenic compounds. Drosophila PGRP-LB belongs to the amidase PGRPs and downregulates the immune deficiency (IMD) pathway by cleaving meso -2,6-diaminopimelic ( meso -DAP or DAP)-type PGN. While the recognition process is well analyzed for the non-catalytic PGRPs, little is known about the enzymatic mechanism for the amidase PGRPs, despite their essential function in immune homeostasis...