Abstract
Tissue resident intestinal macrophages are known to exhibit an anti-inflammatory phenotype and produce little pro-inflammatory cytokines upon TLR ligation, allowing symbiotic co-existence with the intestinal microbiota. However, upon acute events such as epithelial damage and concomitant influx of microbes, these macrophages must be able to quickly mount a pro-inflammatory response while more inflammatory macrophages are recruited from the blood stream simultaneously. Here, we show that dietary intake of vitamin A is required for the maintenance of the anti-inflammatory state of tissue resident intestinal macrophages. Interestingly, these anti-inflammatory macrophages were characterized by high levels of Dectin-1 expression. We show that Dectin-1 expression is enhanced by the vitamin A metabolite retinoic acid and our data suggests that Dectin-1 triggering might provide a switch to induce a rapid production of pro-inflammatory cytokines. In addition, Dectin-1 stimulation resulted in an altered metabolic profile which is linked to a pro-inflammatory response. Together, our data suggests that presence of vitamin A in the small intestine enhances an anti-inflammatory phenotype as well as Dectin-1 expression by macrophages and that this anti-inflammatory phenotype can rapidly convert toward a pro-inflammatory state upon Dectin-1 signaling.
Highlights
Macrophages are mostly tissue-resident mononuclear phagocytes that have a tissue-specific role besides immune surveillance and clearing of pathogens
We observed a decrease in CD11bhighCX3CR1+CD45+ cells, which include anti-inflammatory macrophages, in the small intestines of vitamin A deficient (VAD) mice compared to vitamin A competent (VAC) mice while the proportion of F4/80+ CD45+ cells, which includes macrophages and monocytes, eosinophils and some dendritic cell subsets, remained unaffected (Figures 1A,B)
We observed that the expression of Arginase-1 and IL-10 was reduced in VAD mice compared to VAC mice while the expression of IL-12 was enhanced in VAD mice (Figures 1C–E)
Summary
Macrophages are mostly tissue-resident mononuclear phagocytes that have a tissue-specific role besides immune surveillance and clearing of pathogens. Macrophages are plastic cells that can either have pro- or anti-inflammatory properties. It is not clear how individual macrophages switch between these phenotypes [1]. To address their inflammatory versus regenerative properties, macrophages are often characterized as either pro-inflammatory M1 macrophages or anti-inflammatory M2 macrophages, which are two ends of a broad spectrum [2]. Whereas anti-inflammatory macrophages use oxidative phosphorylation for ATP production, pro-inflammatory macrophages rely on glycolysis for the rapid production of ATP and biosynthetic intermediates necessary for the production of pro-inflammatory cytokines and reactive oxygen species [8, 9]. Macrophages within the tissues can have a broad spectrum of functions, of which the pro-inflammatory M1 and anti-inflammatory M2 classification is an artificial representation of this range of functionalities
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