Butyrate enhances antibacterial effects while suppressing other features of alternative activation in IL-4-induced macrophages

• DOI: 10.1152/ajpgi.00440.2015
• Publication Date: 2016-03-25T04:13:23Z
• Authors: Maria R. Fernando; Alpana Saxena; José-Luis Reyes; Derek M. McKay
• Keywords: Proinflammatory cytokine; Short-chain fatty acid

The short-chain fatty acid butyrate is produced by fermentation of dietary fiber the intestinal microbiota; primary energy source colonocytes and has immunomodulatory effects. Having shown that macrophages differentiated with IL-4 [M(IL-4)s] can suppress colitis, we hypothesized would reinforce an M(IL-4) phenotype. Here, show in presence M(IL-4)s display reduced expression their hallmark markers Arg1 Ym1 significantly suppressed LPS-induced nitric oxide, IL-12p40, IL-10 production. Butyrate treatment likely altered phenotype via inhibition histone deacetylation. Functionally, treated showed increased phagocytosis killing bacteria, compared this was not accompanied enhanced proinflammatory cytokine Culture regulatory T cells M(IL-4 + butyrate)s revealed both macrophage subsets T-cell marker Foxp3. However, Tregs cocultured butyrate) less IL-17A than M(IL-4). These data illustrate importance butyrate, a microbial-derived metabolite, regulation gut immunity: demonstration promotes limit production reveals novel aspects bacterial-host interaction homeostasis.