Endosymbiont control through non-canonical immune signaling and gut metabolic remodeling

Animals coexist with bacteria and need to keep these microorganisms under tight control. To achieve such control, pattern recognition receptors (PRRs) sense bacterial cues and induce the production of antimicrobials. Here, we uncover a metabolic arm in the control of symbionts by PRRs. We show that, in Drosophila, the PRRs PGRP-LC and PGRP-LE act independently of canonical NF-κB signaling to repress essential metabolic functions in the gut, such as digestion and central carbon metabolism. This metabolic switch affects commensal populations and drastically reduces intestinal and systemic populations of the intracellular parasite Wolbachia. We propose that intestinal metabolic remodeling complements immune responses by imposing nutrient restriction on intracellular bacteria, whose lifestyle protects them from antimicrobials. Our findings reveal a role for PRRs in bacterial control beyond canonical immune pathways and provide insights into how microbial signals modulate symbiotic populations but also nutrition and metabolism in animals.