The road to Toll

A few years ago, it would have been difficult to argue that elucidating the mechanisms of disease resistance in the fruit fly, Drosophila melanogaster, would provide new insights into mammalian immunity. Yet the finding that the Drosophila protein Toll mediates immune responses to fungal infection had a pioneering role in the identification of Toll-like receptors as essential regulators of mammalian host defence, and it fundamentally altered our understanding of innate immunity. In this Landmark article, I describe the thought processes and the experimental steps that defined Toll as a key regulator of Drosophila immune responses

Insect Immunity: The Post-Genomic Era

SummaryInsects have a complex and effective immune system, many components of which are conserved in mammals. But only in the last decade have the molecular mechanisms that regulate the insect immune response—and their relevance to general biology and human immunology—become fully appreciated. A meeting supported by the Centre National de la Récherche Scientifique (France) was held to bring together the whole spectrum of researchers working on insect immunity. The meeting addressed diverse aspects of insect immunity and brought together geneticists working on Drosophila melanogaster with those working on other insects

Dynamic Evolution of Antimicrobial Peptides Underscores Trade-Offs Between Immunity and Ecological Fitness

This work is licensed under a Creative Commons Attribution 4.0 International License.There is a developing interest in how immune genes may function in other physiological roles, and how traditionally non-immune peptides may, in fact, be active in immune contexts. In the absence of infection, the induction of the immune response is costly, and there are well-characterized trade-offs between immune defense and fitness. The agents behind these fitness costs are less understood. Here we implicate antimicrobial peptides (AMPs) as particularly costly effectors of immunity using an evolutionary framework. We describe the independent loss of AMPs in multiple lineages of Diptera (true flies), tying these observations back to life history. We then focus on the intriguing case of the glycine-rich AMP, Diptericin, and find several instances of loss, pseudogenization, and segregating null alleles. We suggest that Diptericin may be a particularly toxic component of the Dipteran immune response lost in flies either with reduced pathogen pressure or other environmental factors. As Diptericins have recently been described to have neurological roles, these findings parallel a developing interest in AMPs as potentially harmful neuropeptides, and AMPs in other roles beyond immunity

The host defense of Drosophila melanogaster

To combat infection, the fruit fly Drosophila melanogaster relies on multiple innate defense reactions, many of which are shared with higher organisms. These reactions include the use of physical barriers together with local and systemic immune responses. First, epithelia, such as those beneath the cuticle, in the alimentary tract, and in tracheae, act both as a physical barrier and local defense against pathogens by producing antimicrobial peptides and reactive oxygen species. Second, specialized hemocytes participate in phagocytosis and encapsulation of foreign intruders in the hemolymph. Finally, the fat body, a functional equivalent of the mammalian liver, produces humoral response molecules including antimicrobial peptides. Here we review our current knowledge of the molecular mechanisms underlying Drosophila defense reactions together with strategies evolved by pathogens to evade them

Stop press: genes that fight infections: what the drosophila genome says about animal immunity

From deciphering the principles of heredity to identifying the genes that control development, the fruit fly Drosophila melanogaster is being used to deconstruct an increasing number of biological processes. Genetic studies of Drosophila responses to microbial infection have identified regulators of innate immunity that are functionally conserved in mammals. These recent findings highlight the ancient origins of animal immune responses and demonstrate the potential of Drosophila for dissecting host-pathogen interactions. The sequencing of the Drosophila genome both enhances genetic approaches and provides new clues for the identification of key components of innate immunity. This article summarizes how information gained from genomic analysis contributes to our understanding of how animals cope with infectious disease

Insect-microbe interactions: the good, the bad and the others

No abstract available

Drosophila immunity: methods for monitoring the activity of Toll and Imd signaling pathways

Invertebrates lack an adaptive immune system and rely on innate immunity to resist pathogens. The response of Drosophila melanogaster to bacterial and fungal infections involves two signaling pathways, Toll and Imd, both of which activate members of the nuclear factor (NF)-kappaB family of transcription factors, leading to antimicrobial peptide (AMP) gene expression. In this chapter, we present the current methods used in our laboratory to monitor the activity of both signaling pathways

Structure and metabolism of peptidoglycan and molecular requirements allowing its detection by the Drosophila innate immune system

Peptidoglycan (murein) is a major essential and specific constituent of the bacterial cell wall. Its main function is to protect cells against the internal osmotic pressure and to maintain the characteristic cell shape. It also serves as a platform for the anchoring of specific proteins and other cell wall components. This giant macromolecule is composed of long glycan chains cross-linked by short peptides. Any alteration of the disaccharide-peptide basic unit results in a global change of peptidoglycan structure and properties. Such global variations are encountered in nature as conserved variations along phyletic lines but have sometimes been acquired as a result of mutations or as a mechanism of resistance against cell-wall targeted antibiotics. During bacterial cell growth and division, the peptidoglycan mesh is constantly broken down by a set of highly specific hydrolases in a maturation process allowing insertion of newly synthesized units in the pre-existing polymerized material. Depending on the bacterial species considered, degradation fragments are either released in the growth medium or efficiently re-utilized for synthesis of new murein in a sequence of events termed the recycling pathway. Peptidoglycan is one of the main pathogen-associated molecular patterns recognized by the host innate immune system. Variations of the structure and metabolism of this cell wall component have been exploited by host defense mechanisms for detection/identification of invading bacterial species. Modification of the peptidoglycan structure could also represent a mechanism allowing bacteria to escape these host defense systems