Bacteria-Derived Peptidoglycan Triggers a Noncanonical Nuclear Factor-κB-Dependent Response in Drosophila Gustatory Neurons.

Probing the external world is essential for eukaryotes to distinguish beneficial from pathogenic micro-organisms. If it is clear that the main part of this task falls to the immune cells, recent work shows that neurons can also detect microbes, although the molecules and mechanisms involved are less characterized. In Drosophila, detection of bacteria-derived peptidoglycan by pattern recognition receptors of the peptidoglycan recognition protein (PGRP) family expressed in immune cells triggers nuclear factor-κB (NF-κB)/immune deficiency (IMD)-dependent signaling. We show here that one PGRP protein, called PGRP-LB, is expressed in bitter gustatory neurons of proboscises. In vivo calcium imaging in female flies reveals that the PGRP/IMD pathway is cell-autonomously required in these neurons to transduce the peptidoglycan signal. We finally show that NF-κB/IMD pathway activation in bitter-sensing gustatory neurons influences fly behavior. This demonstrates that a major immune response elicitor and signaling module are required in the peripheral nervous system to sense the presence of bacteria in the environment.SIGNIFICANCE STATEMENT In addition to the classical immune response, eukaryotes rely on neuronally controlled mechanisms to detect microbes and engage in adapted behaviors. However, the mechanisms of microbe detection by the nervous system are poorly understood. Using genetic analysis and calcium imaging, we demonstrate here that bacteria-derived peptidoglycan can activate bitter gustatory neurons. We further show that this response is mediated by the PGRP-LC membrane receptor and downstream components of a noncanonical NF-κB signaling cascade. Activation of this signaling cascade triggers behavior changes. These data demonstrate that bitter-sensing neurons and immune cells share a common detection and signaling module to either trigger the production of antibacterial effectors or to modulate the behavior of flies that are in contact with bacteria. Because peptidoglycan detection doesn't mobilize the known gustatory receptors, it also demonstrates that taste perception is much more complex than anticipated.

How Bacteria Impact Host Nervous System and Behaviors: Lessons from Flies and Worms.

Behavior is the neuronally controlled, voluntary or involuntary response of an organism to its environment. An increasing body of evidence indicates that microbes, which live closely associated with animals or in their immediate surroundings, significantly influence animals' behavior. The extreme complexity of the nervous system of animals, combined with the extraordinary microbial diversity, are two major obstacles to understand, at the molecular level, how microbes modulate animal behavior. In this review, we discuss recent advances in dissecting the impact that bacteria have on the nervous system of two genetically tractable invertebrate models, Drosophila melanogaster and Caenorhabditis elegans.