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

Abstract

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 spätzle. 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.

Influence of RVFV Infection on Olfactory Perception and Behavior in Drosophila melanogaster

“…Similarly, increased locomotor activity in DENV infected mosquitoes was also ascribed to infection-based changes in the insect's clock [84]. In Drosophila, influence of an infection on activity patterns and the circadian clock have been shown as well [85][86][87]. Remarkably, the rhythmicity of the circadian activity pattern in DENV infected mosquitoes was similar to that of uninfected mosquitoes [84]; this matches our observations for RVFV infected flies.…”

Transcriptional profiling ofDrosophilamale-specific P1 (pC1) neurons

“…This raises the question: why are immuneresponse genes upregulated following courtship interactions? One possibility is that courtship is inherently risky, requiring close contact with individuals harboring potential pathogens (bacteria, fungi, viruses, and parasites) (89) and these commensal microorganisms can directly impact neuronal function and behavior (90–94). The risk, and impact, of infection may have driven flies to evolve countermeasures.…”

Mitochondrial background can explain variable costs of immune deployment

“…For example, immune stimulation by LPS resulted in a marked decrease in locomotor activity in mice up to 36 hours post inoculation [44] and Eurasian collared dove nestlings injected with LPS had reduced lifespans as a result of predation, which was likely due to reduced activity levels [9]. In contrast, injection with heat-killed Micrococcus luteus , a Gram-positive bacterium, induced an increase in activity levels in D. melanogaster [12]. Thus, immune activation sometimes comes with significant costs, manifested as behavioural changes, but these tend to be context dependent [45,46] as was evident in the current study.…”

“…For instance, there is a strong negative relationship between immune function and reproductive success across species [6], while in many species there is evidence that immune deployment can be costly in terms of reduced longevity [3,[7][8][9]. Additionally, immune activation can trigger significant behavioural changes, such as in locomotor activity, that are intimately intertwined with host energy intake and reallocation [10][11][12]. Even prokaryotic organisms, which lack what is usually considered to be a conventional immune system, have shown that those with strong pathogen defence mechanisms may experience reduced growth rates [13,14].…”