During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia. In healthy flies, suppressing immunity in glial cells resulted in increased adipokinetic hormonal signaling with high nutrient levels in later life and an extension of active lifespan. Thus, when levels of IMD/NF-κB deviate from normal, two mechanisms are at play: lower levels derepress an immune-endocrine axis, which mobilizes nutrients, leading to lifespan extension, whereas higher levels increase antimicrobial peptides, causing neurodegeneration. Immunity in the fly brain is therefore a key lifespan determinant.

Summary: Innate immunity relies entirely upon germ-line encoded receptors, signalling components and effector molecules for the recognition and elimination of invading pathogens. The fruit fly Drosophila melanogaster with its powerful collection of genetic and genomic tools has been the model of choice to develop ideas about innate immunity and host–pathogen interactions. Here, we review current research in the field, encompassing all layers of defence from the role of the microbiota to systemic immune activation, and attempt to speculate on future directions and open questions.

Alzheimer’s disease (AD) is the most common form of dementia, an eversible, progressive disease that causes problems with memory, thinking, language, planning, and behavior. There are a number of risk factors associated with developing AD but the exact cause remains unknown. The predominant theory is that excessive build-up of amyloid protein leads to cell death, brain atrophy, and cognitive and functional decline. However, the amyloid hypothesis has not led to a single successful treatment. The recent failure of Solanezumab, a monoclonal antibody to amyloid, in a large phase III trial was emblematic of the repeated failure of anti-amyloid therapeutics. New disease targets are urgently needed. The innate immune system is increasingly being implicated in the pathology of number of chronic diseases. This focused review will summarize the role of transcription factor nuclear factor-kappa B (NF-κB), a key regulator of innate immunity, in the major genetic and environmental risk factors in cellular, invertebrate and vertebrate models of AD. The paper will also explore the relationship between NF-κB and emerging environmental risk factors in an attempt to assess the potential for this transcription factor to be targeted for disease prevention.

Following cultivation-dependent and -independent techniques, we investigated the microbiota associated withBactrocera oleae, one of the major agricultural pests in olive-producing countries. Bacterial 16S rRNA gene libraries and ultrastructural analyses revealed the presence of several bacterial taxa associated with this insect, among whichAcetobacter tropicaliswas predominant. The recent increased detection of acetic acid bacteria as symbionts of other insect model organisms, such asAnopheles stephensi(G. Favia et al., Proc. Natl. Acad. Sci. USA 104:9047-9051, 2007) orDrosophila melanogaster(C. R. Cox and M. S. Gilmore, Infect. Immun. 75:1565-1576, 2007), prompted us to investigate the association established betweenA. tropicalisandB. oleae. Using anA. tropicalis-specific PCR assay, the symbiont was detected in all insects tested originating from laboratory stocks or field-collected from different locations in Greece. This acetic acid bacterium was successfully established in cell-free medium, and typing analyses, carried out on a collection of isolates, revealed that differentA. tropicalisstrains are present in fly populations. The capability to colonize and lodge in the digestive system of both larvae and adults and in Malpighian tubules of adults was demonstrated by using a strain labeled with a green fluorescent protein.

Imaging of biological matter across resolution scales entails the challenge of preserving the direct and unambiguous correlation of subject features from the macroscopic to the microscopic level. Here, we present a correlative imaging platform developed specifically for imaging cells in 3D under cryogenic conditions by using X-rays and visible light. Rapid cryo-preservation of biological specimens is the current gold standard in sample preparation for ultrastructural analysis in X-ray imaging. However, cryogenic fluorescence localization methods are, in their majority, diffraction-limited and fail to deliver matching resolution. We addressed this technological gap by developing an integrated, user-friendly platform for 3D correlative imaging of cells in vitreous ice by using super-resolution structured illumination microscopy in conjunction with soft X-ray tomography. The power of this approach is demonstrated by studying the process of reovirus release from intracellular vesicles during the early stages of infection and identifying intracellular virus-induced structures.

Drosophila has a blood system with three types of haemocytes which function throughout different developmental stages and environmental stimuli. Haemocytes play essential roles in tissue modelling during embryogenesis and morphogenesis, and also in innate immunity. The open circulatory system of Drosophila makes haemocytes ideal signal mediators to cells and tissues in response to events such as infection, wounding and tumour formation. In this context, Drosophila is now used for screening and investigation of genes implicated in human leukaemia and also in modelling development of solid tumours. This line of research offers promising opportunities to determine the seemingly conflicting roles of blood cells in tumour progression and invasion. This review provides an overview of the signalling pathways conserved in Drosophila during haematopoiesis, haemostasis, innate immunity, wound healing and inflammation. We also review the most recent progress in the use of Drosophila as a cancer research model with an emphasis on the roles haemocytes can play in various cancer models and in the links between inflammation and cancer.