Most of us can tell when we're coming down with something. At the first sign of illness, we lose our appetites, become lethargic and begin to feel cold. This suite of behaviours, often referred to as sickness behaviour, is thought to limit the spread of infection within, and between, individuals and is easily recognised in under-the-weather humans. Michael Pankratz and colleagues from the University of Bonn, Germany, wondered whether poorly insects may also go off their tea when they pick up an infection. Intrigued by the possibility, Pankratz and Benjamin Wäschle set about trying to make fruit fly larvae sick by feeding them an infected snack.
However, Pankratz recalls that encouraging the larvae to consume infectious Pseudomonas entomophila was problematic. ‘We tried choice assays, different agar conditions, yeast conditions, different larval stages, even adults’, says Pankratz, who only succeeded in getting the larvae to consume a diseased dinner when there was no alternative. Providing larvae with one of three dining opportunities – yeast (their preferred diet), yeast mixed with dead non-toxic bacteria and yeast mixed with the live bacteria – Sandya Surendran filmed the larvae and saw that they were content to remain in place when consuming the first two (uninfected) meals over a 12 h period. In contrast, the larvae that were served with infected yeast chose to move on, but they were expressing more than a simple aversion. Larvae that simply wish to avoid an unpleasant flavour take immediate action; however, the larvae that were provided with infected yeast only began moving away in search of uncontaminated food after 2–3 h, with 80% of the animals evading the infected food 12 h later. The larvae were also able to identify, and avoid, the yeast that was infected with live bacteria, while they were happy to chomp on the dead bacteria mix that presented no risk. However, when Surendran served infected yeast to ravenous larvae, half of the insects were prepared to risk picking up an infection in favour of a good dinner.
Having discovered that fruit fly larvae can recognise infected food, Pankratz wondered whether hugin neurons, which relay sensory information to the animals’ brains, might be involved in their aversive reaction. ‘We knew that activating neurons that express the hugin neuropeptide can downregulate feeding, as well as inducing wandering behaviour’, says Pankratz. Could the circuit lie at the heart of the larvae's discerning behaviour?
After disabling the larvae's hugin neurons and presenting the insects with an infected meal, Surendran found that the impaired larvae left the patch of infected yeast much more slowly. And when she reduced the amount of hugin produced by the larvae, they were as active as untreated larvae, but less sensitive to the infection lurking in their lunch.
As hugin neurons relay signals from bitter taste interneurons to the larval brain centres, Pankratz wondered whether the larvae are using a clever taste trick to avoid a toxic treat. Sebastian Hückesfeld measured the calcium activity in the neurons after the larvae had been offered either live or dead bacteria, in addition to measuring the levels of the hugin neuropeptide in the neurons, and found that both were elevated after an infectious meal. ‘Our idea is that activating the hugin neurons makes the animals “think” that they are tasting bitter food’, says Pankratz,
So it seems that Drosophila larvae perform their own variety of sickness behaviour, and Pankratz says, ‘Even lower organisms are capable of startling highly sophisticated evasion programs to protect themselves from sickness’.