Mitochondrial-derived glutamate dictates resistance to pathogen infection through vitamin-dependent metabolic remodeling

The functional integration of innate immune and metabolic signaling responses represents an ancient strategy to manage infections in metazoans. Using Drosophila, we uncovered that immune-metabolic sensing in muscle dictates resistance to enteric bacterial infection through vitamins dependent metabolic remodeling. Within muscle, the activation strength of systemic innate immune signaling, integrated with mitochondrial-dependent glutamate dehydrogenase (Gdh) function, conditions lipid mobilization from adipose. Mild intramuscular IMD/innate immune signaling activity allows for infection-mediated increases in mitochondrial biogenesis/function, which further stimulates mitochondria/Gdh-dependent synthesis of glutamate. Intramuscular derived glutamate acts as a systemic metabolite to influence lipid mobilization through altering vitamin metabolism. This lipid mobilization improves bacterial clearance and boost infection resistance. Conversely, elevated activation of IMD/innate immune signaling in muscle impedes infection-mediated increases in mitochondrial biogenesis/function and subsequent metabolic remodeling. Finally, life history traits that fine-tune intramuscular mitochondrial dynamics consequently influence infection resistance and shape phenotypic diversity of infection responses within populations. We wanted to explore the muscle and adipose transcriptional networks in response to enteric bacterial infection. Utilizing transcriptomics (RNA-seq.), we generated genome-wide expression profiles from dissected thoraces/muscle and carcass/fat body of Act88FGal4>UAS-RelishRNAi flies upon Mock (sucrose) or Pseudomonas entomophila (P.e.) oral infection (compared to controls [Act88FGal4>w1118), and also drosocin-GFP (Dro-GFP) flies upon Mock (sucrose) or P.e. oral infection (Dro-GFP Positive and Dro-GFP Negative).