Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster

Host behavioural changes are among the most apparent effects of infection. 'Sickness behaviour' can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here, using a real-time tracking and behavioural profiling platform, we show that in Drosophila melanogaster, several systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in some lethal infections. Using multiple bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spatzle. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of both Toll and the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response. Non-technical author summarySickness behaviours are often observed during infection. Animals have been shown to change their feeding, mating, social and resting (sleeping) behaviours in response to infection. We show here that fruit-flies infected with bacteria respond by increasing their physical activity and decreasing the amount of time spent sleeping. This increase in activity is seen in some, but not all, bacterial infections, and appears to be driven by at least two different mechanisms: with some bacteria, activating the immune response is the only requirement to induce increased activity, while other bacteria induce increased activity independently of known immune detection pathways. The biological role of increased activity is unclear; flies in the wild may be driven to flee sites where infection risk or pathogen burden is high. Alternatively, increased activity could serve a less direct anti-microbial function. For example, active animals may be more likely to encounter potential mates or food resource.

Automated summary

Host behavioural changes are a common response to infection, including increased physical activity. Different mechanisms may drive the increased activity in different bacterial infections, some requiring immune response and others being independent of known immune detection pathways. This increased activity could be an important aspect of the host response.