The immune response attenuates growth and nutrient storage in Drosophila by reducing insulin signaling.
Innate immunity is the primary and most ancient defense against infection. Although critical to survival, coordinating protection against a foreign organism is energetically costly, creating the need to reallocate substrates from nonessential functions, such as growth and nutrient storage. However, the mechanism by which infection or inflammation leads to a reduction in energy utilization by these dispensable processes is not well understood. Here, we demonstrate that activation of the Toll signaling pathway selectively in the fat body, the major immune and lipid storage organ of the fruit fly, Drosophila melanogaster, leads to both induction of immunity and reallocation of resources. Toll signaling in the fat body suppresses insulin signaling both within these cells and non-autonomously throughout the organism, leading to a decrease in both nutrient stores and growth. These data suggest that communication between these two regulatory systems evolved as a means to divert energy in times of need from organismal growth to the acute requirement of combating infection.
DiAngelo
Justin R
JR
The Institute for Diabetes, Obesity and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Bland
Michelle L
ML
Bambina
Shelly
S
Cherry
Sara
S
Birnbaum
Morris J
MJ
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology / Q000254:growth & development* / Q000276:immunology* / Q000382:microbiology; D005216:Fat Body / Q000166:cytology / Q000276:immunology; D005260:Female; D005502:Food; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007109:Immunity / Q000276:immunology*; D007328:Insulin / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction / Q000276:immunology*; D013347:Subcellular Fractions / Q000378:metabolism; D051193:Toll-Like Receptors / Q000276:immunology
D029721:Drosophila Proteins; C477334:FOXO protein, Drosophila; D051858:Forkhead Transcription Factors; D007328:Insulin; D051193:Toll-Like Receptors; C439909:imd protein, Drosophila; D019869:Phosphatidylinositol 3-Kinases