Intestinal Macrophages Balance Inflammatory Expression Profiles via Vitamin A and Dectin-1-Mediated Signaling

Abstract

Tissue resident intestinal macrophages are known to exhibit an anti-inflammatory phenotype and produce little pro-inflammatory cytokines upon TLR ligation, allowing symbiotic coexistence 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 antiinflammatory 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.

Sphingomyelin Biosynthesis Is Essential for Phagocytic Signaling during Mycobacterium tuberculosis Host Cell Entry

“…Why dectin-1 levels in macrophages are not affected by a loss of sphingolipids remains to be established. However, it is well known that the expression profiles of pattern recognition receptors vary considerably among different types of immune cells (54), and that macrophages expose a higher number of dectin-1 receptors on their surface than dendritic cells (55,56). As these cell types likely also have different lipid compositions, it is conceivable that a block in sphingolipid biosynthesis differentially affects dectin-1 trafficking and/or turnover.…”

A novel hypothesis for COVID-19 pathogenesis: Retinol depletion and retinoid signaling disorder

“…Retinol induces the T cell activation through CD3 likely through non-genomic activity of membrane bound RAR [185] . VitA also has an anti-inflammatory effect that is required for maintaining intestinal immune tolerance [68] , [186] , [187] . VitA deficiency (VAD)is associated with inflammation and dietary intake of VitA is required for the maintenance of the anti-inflammatory state of tissue-resident intestinal macrophages [68] , [188] .…”

“…Depletion of retinol causes a transition from a proper innate immune response to the exacerbated cytokine storm [41] . In this way, RA signaling acts as a switch in balancing the innate and adaptive immune response [186] and the signaling for this switch is provided by ATRA [280] . Therefore, we believe that the immune system dysregulation and the biphasic immunological pathogenesis of COVID-19 are associated with retinoid signaling disorder.…”

The Involvement of the Chemokine RANTES in Regulating Luminal Acidification in Rat Epididymis

“…In addition to their classical function in immune system, the non-classical function of macrophage in peripheral, non-lymphoid organs has been widely investigated (13). For example, in the small intestinal mucosal system (14,15), macrophages can stretch out their long protuberances to the intestinal lumen to monitor the luminal composition changes so as to regulate the absorption of nutrients and secretion of goblet cells by interacting with intestinal epithelial cells (16,17). Similar to the intestinal tract, macrophages in the initial segment of epididymis also extend long slender projections to the epididymal lumen to sample the fluid components in the lumen (18,19).…”