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| Status |
Public on Jun 02, 2021 |
| Title |
Gut-derived inflammatory cytokines modulate olfactory perception through metabolic reprogramming of ensheathing glia. |
| Organism |
Drosophila melanogaster |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Infection-induced aversion against enteropathogens is a conserved sickness behavior that can promote host survival1-3. The etiology of this behavior remains poorly understood, but studies in Drosophila have linked olfactory and gustatory perception to avoidance behaviors against toxic microbes4-6. Whether and how enteric infections directly influence sensory perception to induce or modulate such behaviors remains unknown. Here we show that enteropathogen infection in Drosophila can modulate olfactory perception through metabolic reprogramming of ensheathing glia of the antennal lobe. This reprogramming depends on JAK/STAT signaling activation in ensheathing glia as a consequence of infection-induced Unpaired cytokine expression in the intestine. JAK/STAT signaling induces the expression of glial monocarboxylate transporters (MCTs) and the apolipoprotein glial lazarillo (Glaz), resulting in changes in glial lipid metabolism. This modulates olfaction sensitivity, promoting avoidance of bacteria-laced food and increasing animal survival. While transient in young animals, gut-induced metabolic reprogramming of ensheathing glia becomes constitutive in old animals due to age-related intestinal inflammation, contributing to an age-related decline in olfaction sensitivity. Our findings identify adaptive glial metabolic reprogramming by gut-derived cytokines as a mechanism causing lasting changes in neuronal activity in the aging animal.
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| Overall design |
We have labelled pan glia of Drosophila with tdTomato in the presence of repo::Gal4 driver, and have further purified STAT::GFP+ glia and STAT::GFP- glia correspondingly from mock or infected young flies.
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| Contributor(s) |
Cai XT, Li H, Jensen MB, Maksoud E, Borneo J, Liang Y, Quake SR, Luo L, Haghighi P, Jasper H |
| Citation(s) |
34290404 |
| Submission date |
Mar 09, 2021 |
| Last update date |
Aug 12, 2021 |
| Contact name |
Jason A Hackney |
| E-mail(s) |
hackney.jason@gene.com
|
| Organization name |
Genentech, Inc.
|
| Department |
Department of Bioinformatics and Computational Biology
|
| Street address |
1 DNA Way
|
| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL25244 |
Illumina NovaSeq 6000 (Drosophila melanogaster) |
|
| Samples (16)
|
| GSM5145604 |
SAM24363089 3d Mock StatGFP positive-4 |
| GSM5145605 |
SAM24363090 3d Mock StatGFP negative-1 |
| GSM5145606 |
SAM24363091 3d Mock StatGFP negative-2 |
| GSM5145607 |
SAM24363092 3d Mock StatGFP negative-3 |
| GSM5145608 |
SAM24363093 3d Mock StatGFP negative-4 |
| GSM5145609 |
SAM24363094 3d Ecc15 StatGFP positive-1 |
| GSM5145610 |
SAM24363095 3d Ecc15 StatGFP positive-2 |
| GSM5145611 |
SAM24363096 3d Ecc15 StatGFP positive-3 |
| GSM5145612 |
SAM24363097 3d Ecc15 StatGFP positive-4 |
| GSM5145613 |
SAM24363098 3d Ecc15 StatGFP negative-1 |
| GSM5145614 |
SAM24363099 3d Ecc15 StatGFP negative-2 |
| GSM5145615 |
SAM24363100 3d Ecc15 StatGFP negative-3 |
| GSM5145616 |
SAM24363101 3d Ecc15 StatGFP negative-4 |
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| Relations |
| BioProject |
PRJNA708213 |
| SRA |
SRP309939 |
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