GSE160652
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. Overall design: 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).