Neural/Immune/Behavioural interactions: Mechanisms, functions and exploitation by parasites

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Animals, including humans, sometimes suppress their ability to resist disease. This suppression is frequently considered dysfunctional, even though it exists in animals across phyla, and is induced using similar molecular pathways. I make the novel suggestion that these changes reflect a reconfiguration of the immune system. This reconfiguration may not produce maximal disease resistance, but it produces the best level of protection possible when resources are shunted towards other physiological systems (e.g. fight-or-flight or reproduction). To test this hypothesis, my students and I will examine the effects of predator stress on the immune system of the caterpillar, Manduca sexta. We will quantify the shift to a pro-inflammatory state, and test whether this state is important for maintaining disease resistance when stress responses are activated. We will test whether disease resistance during chronic predator stress is reduced even further when stress-induced changes on the immune system are prevented. In addition, we will use adult female crickets (Gryllus texensis) to test whether a shift to a more pro-inflammatory state with age enhances reproductive success. We will assess whether glutathione, an important antioxidant in insects, is at the centre of a physiological trade-off between reproduction and immune function. Age-related changes in immune function prior to senescence may reflect a shift away from self-maintenance and towards reproduction. Finally, we will test whether insect immune systems send chemical signals (i.e. cytokines) to the nervous system, to support our hypothesis of an integrated immune-neural network. We will use the ability of some parasites to change host behaviour by altering host cytokine production to demonstrate this connection. We will test whether the insect cytokine, plasmatocyte spreading peptide, affects neural function in the brain of M. sexta. Our study will be the first to demonstrate that an insect cytokine affects neural activity.Novelty and Expected Impact of the Proposal. We will use advanced statistical techniques (e.g. structural equation models) to integrate our behavioural, physiological, biochemical, and genomic data. This integration will make it possible to show how and why neural-immune interactions can be beneficial, even if disease resistance appears to be reduced. This research will provide a significant advance by demonstrating how reconfiguration of physiological networks can provide an explanation for seemingly maladaptive connections. It will be of interest to a broad range of biologists (e.g. behavioural physiologists, behavioural ecologists and ecoimmunologists). This research also has the potential to be of practical importance, by raising the possibility that prolonged pro-inflammatory states could have value.