The hepcidin-ferroportin axis controls the iron content of Salmonella-containing vacuoles in macrophages

Nature Communications
Daejin LimHyon E Choy

Abstract

Macrophages release iron into the bloodstream via a membrane-bound iron export protein, ferroportin (FPN). The hepatic iron-regulatory hormone hepcidin controls FPN internalization and degradation in response to bacterial infection. Salmonella typhimurium can invade macrophages and proliferate in the Salmonella-containing vacuole (SCV). Hepcidin is reported to increase the mortality of Salmonella-infected animals by increasing the bacterial load in macrophages. Here we assess the iron levels and find that hepcidin increases iron content in the cytosol but decreases it in the SCV through FPN on the SCV membrane. Loss-of-FPN from the SCV via the action of hepcidin impairs the generation of bactericidal reactive oxygen species (ROS) as the iron content decreases. We conclude that FPN is required to provide sufficient iron to the SCV, where iron serves as a cofactor for the generation of antimicrobial ROS rather than as a nutrient for Salmonella.

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Sep 12, 2018·Pharmaceuticals·Ana Cordeiro GomesMaria Salomé Gomes
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Methods Mentioned

BETA
confocal microscopy
biosensor
MDA
biosensors
fluorescence microscopy
transfection
Fluorescence
carbonylation

Software Mentioned

ImageJ

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