Listening to your gut: immune challenge to the gut sensitizes body wall nociception in the caterpillar Manduca sexta.

Immune-nociceptor connections are found in animals across phyla. Local inflammation and/or damage results in increased nociceptive sensitivity of the affected area. However, in mammals, immune responses far from peripheral nociceptors, such as immune responses in the gut, produce a general increase in peripheral nociceptive sensitivity. This phenomenon has not, to our knowledge, been found in other animal groups. We found that consuming heat-killed pathogens reduced the tactile force needed to induce a defensive strike in the caterpillar Manduca sexta. This increase in the nociceptive sensitivity of the body wall is probably part of the reconfiguration of behaviour and physiology that occurs during an immune response (e.g. sickness behaviour). This increase may help enhance anti-predator behaviour as molecular resources are shifted towards the immune system. This article is part of the Theo Murphy meeting issue 'Evolution of mechanisms and behaviour important for pain'.

Eating when ill is risky: immune defense impairs food detoxification in the caterpillar Manduca sexta.

Mounting an immune response consumes resources, which should lead to increased feeding. However, activating the immune system reduces feeding (i.e. illness-induced anorexia) in both vertebrates and invertebrates, suggesting that it may be beneficial. We suggest that illness-induced anorexia may be an adaptive response to conflicts between immune defense and food detoxification. We found that activating an immune response in the caterpillar Manduca sexta increased its susceptibility to the toxin permethrin. Conversely, a sublethal dose of permethrin reduced resistance to the bacterium Serratia marcescens, demonstrating a negative interaction between detoxification and immune defense. Immune system activation and toxin challenge each depleted the amount of glutathione in the hemolymph. Increasing glutathione concentration in the hemolymph increased survival for both toxin- and immune+toxin-challenged groups. The results of this rescue experiment suggest that decreased glutathione availability, such as occurs during an immune response, impairs detoxification. We also found that the expression of some detoxification genes were not upregulated during a combined immune-toxin challenge, although they were when animals received a toxin challenge alone. These results suggest that immune defense reduces food detoxification capacity. Illness-induced anorexia may protect animals by decreasing exposure to food toxins when detoxification is impaired.