250C Poster - 02. Immunity and the microbiome
Saturday April 09, 1:30 PM - 3:30 PM

Authors:
Krista Grimes ¹; Esteban Beckwith ^1,2; Marc Dionne ¹

Affiliations:
1) MRC Centre for Molecular Bacteriology and Infection, and Department of Life Sciences, Imperial College London; 2) Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), UBA-CONICET, Buenos Aires

Keywords:
j. fat body; b. metabolism

Immunity and metabolism are closely interconnected processes. Mounting an immune response is energetically costly, and therefore relies on metabolism adapting to provide the necessary energy and raw materials. The aim of this work was to further characterise the metabolic changes that occur in Drosophila during bacterial infection. Using Targeted DamID, we found that two metabolic genes with linked roles in amino acid metabolism, astray and Nmdmc, are upregulated in the fat body during infection. astray is a phosphoserine phosphatase that catalyses the final reaction in the de novo production of serine from glycolytic intermediates. Serine can be converted into glycine using a tetrahydrofolate cofactor, which is produced by a cycle of reactions involving Nmdmc. We found that in flies infected with Gram positive bacteria, the upregulation of astray and Nmdmc is dependent on both Dif and FOXO, key components of the Toll and insulin signalling pathways, which may act in a co-ordinated manner. Further, fat body knockdown of the transcription factor MEF2 leads to an increase in the expression of astray and Nmdmc in uninfected flies, suggesting that MEF2 may contribute to the repression of both genes in the absence of infection. We next sought to establish whether astray and Nmdmc play functional roles in supporting the immune response. Fat body specific astray knockdown results in a significant survival defect during Staphylococcus aureus infection, whilst bacterial numbers remain unchanged, indicating that astray contributes to host tolerance. In contrast, knockdown of Nmdmc in the fat body leads to a modest survival increase. Together, these data demonstrate that metabolism is transcriptionally fine-tuned in a manner that has complex impacts on the course and outcome of infection and indicate that regulation of amino acid metabolism via FOXO is critical to support host health during immune responses.