Metabolic control of immune-competency by odors inDrosophila

SUMMARY Drosophila blood-progenitor cells generate an inflammatory cell-type termed lamellocyte, in response to parasitic wasp-infections. In this study we show that olfaction primes lamellocyte potential. Specifically, larval odor-detection mediated release of systemic γ-aminobutyric acid (GABA) from neurosecretory cells, is detected and internalized by blood progenitor-cells. GABA catabolism through the GABA-shunt pathway prevents Sima (HIFα) protein degradation. Sima is necessary and sufficient for lamellocyte induction. However, limited systemic GABA availability during development restricts blood-progenitor Sima levels and consequently their lamellocyte potential. Preconditioning Drosophila larvae in odor environments mimicking parasitoid-threatened conditions raises systemic GABA and blood-progenitor Sima levels. As a result, infection responses in these animals are rapid and efficient. Overall, this study explores the importance of sensory control of myeloid-immunity and unravels the adaptive influence of environmental odor-experience on myeloid-metabolism and priming innate-immune potential.