RRC ID 57429
著者 Yang S, Zhao Y, Yu J, Fan Z, Gong ST, Tang H, Pan L.
タイトル Sugar Alcohols of Polyol Pathway Serve as Alarmins to Mediate Local-Systemic Innate Immune Communication in Drosophila.
ジャーナル 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.
巻・号 26(2)
ページ 240-251.e8
公開日 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
引用数 1
リソース情報
ショウジョウバエ 11992R-1 11992R-2 6084R-1 6084R-3