RESUMEN
This review outlines the known cellular pathways and mechanisms involved in Drosophila age-dependent immunity to pathogenic microorganisms such as bacteria and fungi. We discuss the implication of host signaling pathways such as the Toll, Immune Deficiency (IMD), Janus kinase signal transducer and activator of transcription (JAK/STAT), and Insulin/Insulin Growth Factor/Target of Rapamycin (IIS/TOR) on immune function with aging. Additionally, we review the effects that factors such as sexual dimorphism, environmental stress, and cellular physiology exert on age-dependent immunity in Drosophila. We discuss potential tradeoffs between heightened immune function and longevity in the absence of infection, and we provide detailed tables outlining the various assays and pathogens used in the cited studies, as well as the age, sex, and strains of Drosophila used. We also discuss the overlapping effects these pathways and mechanisms have on one another. We highlight the great utility of Drosophila as a model organism and the importance of a greater focus on age-dependent antiviral immunity for future studies.
RESUMEN
Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its full potential to investigate the response of the aged host to viral infection. Here, we show that, in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House virus due to an age-dependent defect in disease tolerance. Relative to younger individuals, we find that older Drosophila mount transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. We show that loss of disease tolerance to Flock House virus with age associates with a stronger regulation of genes involved in apoptosis, some genes of the Drosophila immune deficiency NF-kB pathway, and genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and furthermore sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age.
