Functional analysis of acetylcholine signaling in Drosophila melanogaster immune response to bacterial pathogens

The cholinergic system, traditionally associated with synaptic neurotransmission in animals, is not restricted to neurons, but is also found in non-neuronal tissues, where it plays important roles in the maintenance of physiological homeostasis. In humans, acetylcholine is involved in the regulation of immune functions, but information about its immunomodulatory potential in invertebrates is still limited. The finding that neonicotinoids, neurotoxic insecticides targeting insect nicotinic acetylcholine receptors (nAChRs), impair the immune response in Drosophila melanogaster and Apis mellifera provided a first hint that acetylcholine signaling may control insect immune pathways. To investigate this issue, we used a Gal4-UAS expression system to alter nAChR function in Drosophila immune tissues and tested if and how these manipulations affected fly survival to pathogen infection. The obtained results support the occurrence of acetylcholine-based immune regulation in Drosophila, whose impact on the fly ability to fight pathogen infections may vary depending on the specific infectious agent.