RESUMEN
Infection-induced aversion against enteropathogens is a conserved sickness behaviour that can promote host survival1,2. The aetiology of this behaviour remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviours against toxic microorganisms3-5. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviours remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfaction through metabolic reprogramming of ensheathing glia of the antennal lobe. Infection-induced unpaired cytokine expression in the intestine activates JAK-STAT signalling in ensheathing glia, inducing the expression of glial monocarboxylate transporters and the apolipoprotein glial lazarillo (GLaz), and affecting metabolic coupling of glia and neurons at the antennal lobe. This modulates olfactory discrimination, promotes the avoidance of bacteria-laced food and increases fly survival. Although transient in young flies, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old flies owing to age-related intestinal inflammation, which contributes to an age-related decline in olfactory discrimination. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism that causes lasting changes in a sensory system in ageing flies.
Asunto(s)
Envejecimiento/metabolismo , Citocinas/metabolismo , Drosophila melanogaster/metabolismo , Intestinos , Neuroglía/metabolismo , Olfato/fisiología , Animales , Reacción de Prevención , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/microbiología , Femenino , Inflamación/metabolismo , Inflamación/microbiología , Intestinos/microbiología , Quinasas Janus/metabolismo , Ácido Láctico/metabolismo , Metabolismo de los Lípidos , Neuronas/metabolismo , Pectobacterium carotovorum , Factores de Transcripción STAT/metabolismo , Transducción de Señal , Tasa de Supervivencia , Factores de Transcripción/metabolismoRESUMEN
Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We characterized 163 distinct cell types and performed an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further developed aging clock models to predict fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find distinctive cell type-specific aging patterns. This atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.