Fine-scale behavioural dynamics separates adaptive sickness behaviour from injury and infection pathology

Abstract

Animals commonly reduce activity during infection, but it remains unclear when such "sickness behaviours" reflect adaptive host regulation versus injury responses or pathogen-driven pathology. We combined high-resolution behavioural phenotyping with experimental partitioning of injury, immune stimulation, and live bacterial infection to dissect these effects in Drosophila melanogaster. Using an outbred fly population, we tracked individual locomotor activity at 1 minute resolution for 400 hours in males and females subjected to one of four treatments: unhandled control, septic injury with buffer, immune stimulation with heat killed Pseudomonas entomophila, or septic infection with live P. entomophila. Across the early post-challenge window, total activity diverged most strongly between the unhandled control and the challenged treatments. Fine-scale analyses revealed that immune challenge primarily reshaped the microstructure of movement: the number of activity bouts changed little, whereas active bout lengths were shorter and inactive periods were modestly prolonged, especially in females. Among infected flies, individuals that died early exhibited a collapse of bout structure, showing prolonged inactivity punctuated by brief, sometimes intense, movements, whereas longer-lived infected flies maintained patterns closer to controls. These behavioural differences were detectable in the very early stages of infection: within the first 24-hours post-infection early-dying flies had both a reduced probability of initiating movement from rest and a reduced probability of sustaining on-going activity, consistent with pathogen-induced debilitation; longer-lived infected flies showed near-normal state-transition profiles. This early suppression of activity in acutely dying males was positively associated with subsequent survival time, suggesting a contribution of adaptive restraint alongside pathology. By resolving fine-scale behaviour and state-transition dynamics, our approach clarifies which aspects of "sickness behaviour" are likely adaptive and which signal pathology.