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 we use a real-time tracking and behavioural profiling platform to show that, in Drosophila melanogaster , many systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in several lethal infections. Using various 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 spätzle and Toll-pathway activity in the fat body and the brain. 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 either spätzle or 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.