Adaptive downregulated liver Recucalcin enhances tolerance defense to intestinal infection by mediating interorgan immunometabolic communication

However, the mechanisms underlying gut-liver communication during intestinal infection, and the key factors linking these processes, remain poorly investigated. In this study, we identified that Regucalcin expression in the remote liver/fat body (Drosophila analogous) is downregulated in response to intestinal infection.

And this adaptive downregulated liver Recucalcin could enhance tolerance defense by limiting intestinal infection-induced lipid wasting. Mechanistically, we uncovered that the loss of Regucalcin facilitated calcium-dependent Dilp6 secretion and suppressed excessive lipid catabolism through the insulin-PI3K-Akt signaling pathway during intestinal infection. Therefore, our work reveals Regucalcin as a novel mediator that orchestrates the cross-talk between the intestine and the liver/fatbody, thereby modulating metabolic tolerance to intestinal infection.