Poisons, Pathogens, And Parasitoids: The Immunophysiological Network Of Manduca Sexta Explored Through Trade-Offs, Microbiome Interactions And Exploitation By The Wasp Cotesia Congregata

Abstract

Animals require sophisticated means of defense against a harsh and constantly changing environment. The immune system, detoxification system, and fight-or-flight responses are generally viewed as disparate systems and studied independently. Recently, the view that these systems are largely independent of one another has been challenged, and thinking has shifted towards the idea of an integrated defense system (IDS) that encompasses all three. Within this system, resources can be shared and borrowed. Different arms of the system can suppress others in order to best deal with the most immediate threat. With this new perspective in mind, I used poisons, pathogens and parasitoids to investigate strategies with which an insect, Manduca sexta, may reconfigure its internal networks in response to differing threats. In addition to the immune, detoxification and stress responses being interconnected, they are additionally networked with the central nervous system (CNS), which controls behaviour. Through investigating the sickness behaviour known as illness-induced anorexia, that is coordinated by the CNS, I show that there is a molecular pinch point between the immune system and the detoxification system. Moreover, I show that this CNS-coordinated change in behaviour may lead to increased survival from an infection by decreasing the need for resources (e.g. glutathione) by the detoxification system. Additionally, the immunophysiological network between two important immune organs, the midgut and fat body, is investigated using biologically relevant stressors. The response to pathogens is time, tissue, and stressor- dependent. Finally, the CNS of Manduca sexta is investigated using proteomic analysis to elucidate whether the parasitic manipulator Cotesia congregata is able to hijack the communication network between the immune system and the CNS. In addition to finding that many different systems and pathways are altered by C. congregata, I also present novel evidence of parasite-coded proteins within the CNS of Manduca sexta. Broadly, this work provides evidence that the arms of the IDS, as well as the CNS, in M. sexta are deeply interconnected and may reconfigure themselves or trade-off resources to most effectively counter immediate threats; but also that this interconnectedness leaves M. sexta susceptible to parasitic manipulation.