Journal
CELL METABOLISM
Volume 33, Issue 12, Pages 2428-+Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2021.10.003
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Funding
- National Institute of Diabetes and Digestive and Kidney Diseases [R01 DK108930]
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Individual hosts within populations exhibit variation in susceptibility to bacterial pathogens, driven by energetic trade-offs and influenced by life history. Immune-metabolic sensing and vitamin-dependent energy substrate reallocation play crucial roles in modulating host-pathogen interactions, ultimately affecting pathogen clearance and host survival. Life history events can shape inter-individual variation in host-pathogen susceptibility after infection.
Individual hosts within populations often show inter-individual variation in their susceptibility to bacterial pathogen-related diseases. Utilizing Drosophila, we highlight that phenotypic variation in host-pathogen susceptibility within populations is driven by energetic trade-offs, facilitated by infection-mediated changes in glutamate metabolism. Furthermore, host-pathogen susceptibility is conditioned by life history, which adjusts immunometabolic sensing in muscles to direct vitamin-dependent reallocation of host energy substrates from the adipose tissue (i.e., a muscle-adipose tissue axis). Life history conditions inter-individual variation in the activation strength of intra-muscular NF-KB signaling. Limited intra-muscular NF-KB signaling activity allows for enhanced infection-mediated mitochondrial biogenesis and function, which stimulates glutamate dehydrogenase-dependent synthesis of glutamate. Muscle-derived glutamate acts as a systemic metabolite to promote lipid mobilization through modulating vitamin B enzymatic cofactor transport and function in the adipose tissue. This energy substrate reallocation improves pathogen clearance and boosts host survival. Finally, life history events that adjust energetic trade-offs can shape inter-individual variation in host-pathogen susceptibility after infection.
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