A body-brain axis between fatbody and brain regulates pathogen avoidance behavior
1 Bonn University
Yujie Wang and Ilona C. Grunwald Kadow University of Bonn, Institute of Physiology, Faculty of Medicine, Bonn, Germany Pathogen ingestion can lead to physiological consequences such as infection and tissue damage. When animals forage, they can learn from negative post-ingestion effects and adapt their behaviors to avoid future exposure. This adaptation of behavior is also referred to as conditioned taste aversion (CTA). While this adaptive behavior of avoiding dangerous food appears conserved across species, the mechanisms remain yet to be fully understood. Emerging evidence suggests that the immune system plays a central role in adaptive behavior. Bacterial peptidoglycans (PGNs), which are present in the bacterial cell wall, are recognized by peptidoglycan-recognizing proteins (PGRPs) in various host tissues, including the nervous system, and trigger the downstream expression of antimicrobial peptides (AMPs) neutralizing these pathogens. Besides this role in the innate immune response, previous studies demonstrated the requirement of AMPs in Pavlovian learning and memory (Barajas-Azpeleta et al., 2018). Our recent work showed that CTA in flies is mediated by a neural circuit involving AMPs and the innate immune receptor PGRP-LC in octopaminergic neurons (invertebrate homologue of noradrenaline) and the insect’s higher brain center, the mushroom body (Kobler et al., 2020). In the present work, we aimed at further elucidating the mechanism underlying this brain-body communication including the specific AMPs involved in the feeding avoidance of the very harmful pathogen Pseudomonas entomophila (Pe). First, our findings reveal the necessity and sufficiency of a specific AMP, Diptericin B. We further show that DiptB is required in OANs as well as in the head fatbody. Interestingly, OANs innervate the fatbody and optogenetic activation of OANs as well as stimulation with octopamine leads to an increase of calcium levels in fatbody cells suggesting a functional synaptic connection between the nervous system and the fatbody. We further show that Dopamine receptor DopR1 is required in specific MB output neurons for learned pathogen avoidance. Surprisingly, dopaminergic neurons are not required and instead dopamine released from the fatbody is necessary. Based on our data, we propose a model wherein pathogen ingestion is detected by immune receptors in OANs and the fatbody that in turn induce the production of AMPs and dopamine from the fatbody. Dopamine then signals to DopR1 in the MB and induces lasting pathogen avoidance. This mechanism provides an efficient signaling pathway between body and brain and, through systemic release of dopamine from the fatbody, modulates all survival relevant behaviors such as pathogen avoidance.