| RRC ID |
57429
|
| Author |
Yang S, Zhao Y, Yu J, Fan Z, Gong ST, Tang H, Pan L.
|
| Title |
Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila.
|
| Journal |
Cell Host Microbe
|
| Abstract |
Interorgan immunological communication is critical to connect the local-systemic innate immune response and orchestrate a homeostatic host defense. However, the factors and their roles in this process remain unclear. We find Drosophila IMD response in guts can sequentially trigger a systemic IMD reaction in the fat body. Sugar alcohols of the polyol pathway are essential for the spatiotemporal regulation of gut-fat body immunological communication (GFIC). IMD activation in guts causes elevated levels of sorbitol and galactitol in hemolymph. Aldose reductase (AR) in hemocytes, the rate-limiting enzyme of the polyol pathway, is necessary and sufficient for the increase of plasma sugar alcohols. Sorbitol relays GFIC by subsequent activation of Metalloprotease 2, which cleaves PGRP-LC to activate IMD response in fat bodies. Thus, this work unveils how GFIC relies on the intermediate activation of the polyol pathway in hemolymph and demonstrates that AR provides a critical metabolic checkpoint in the global inflammatory response.
|
| Volume |
26(2)
|
| Pages |
240-251.e8
|
| Published |
2019-8-14
|
| DOI |
10.1016/j.chom.2019.07.001
|
| PII |
S1931-3128(19)30345-2
|
| PMID |
31350199
|
| MeSH |
Alarmins / immunology*
Aldehyde Reductase / genetics
Aldehyde Reductase / metabolism
Aldo-Keto Reductases / genetics
Animals
Animals, Genetically Modified
Carrier Proteins / metabolism
Drosophila / genetics
Drosophila / immunology*
Fat Body / metabolism
Galactitol / blood
Galactitol / metabolism
Hemolymph / metabolism
Humans
Immunity, Innate / physiology*
Inflammation / immunology
Male
Metalloproteases / metabolism
Polymers / metabolism*
Signal Transduction / immunology
Sorbitol / blood
Sorbitol / metabolism
Sugar Alcohols / blood
Sugar Alcohols / metabolism*
|
| IF |
15.753
|
| Times Cited |
1
|
| Resource |
| Drosophila |
11992R-1
11992R-2
6084R-1
6084R-3 |
