BioProject

In addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. More...

In addition to satisfying the metabolic demands of cells, mitochondrial metabolism helps regulate immune cell function. To date, such cell-intrinsic metabolic-immunologic cross-talk has only been described operating in cells of the immune system. Here we show that epidermal cells utilize fatty acid β-oxidation to fuel their contribution to the immune response during cutaneous inflammation. By live imaging metabolic and immunological processes within intact zebrafish embryos during cutaneous inflammation, we uncover a mechanism where elevated β-oxidation-fueled mitochondria-derived reactive oxygen species within epidermal cells helps guide matrix metalloproteinase-driven leukocyte recruitment. This mechanism requires the activity of a zebrafish homolog of the mammalian mitochondrial enzyme, Immunoresponsive gene 1. This study describes the first example of metabolic reprogramming operating within a non-immune cell type to help control its contribution to the immune response. Targeting of this metabolic-immunologic interface within keratinocytes may prove useful in treating inflammatory dermatoses. In this study, Affymetrix Zebrafish Genome Arrays were used to identify zebrafish Irg1l (a homolog of mammalian IRG1) as a gene up-regulated in response to Salmonella infection. Overall design: The microarray analysis compared 4 day post fertilisation (dpf) dissected larval zebrafish trunks (approximately 50) that had been injected at 2 dpf with either: (i) PBS (as a negative control) or (ii) live Salmonella enterica serovar Typhimurium bacteria. The study was performed in triplicate. Less...