Lactate and short chain fatty acids modulate TLR-mediated activation of epithelial and myeloid cells in vitro

Short chain fatty acids (SCFA) are produced by intestinal microbiota in the large intestine where they can interact with players of innate immune response. In order to determine if SCFA (butyrate, propionate, acetate and lactate) can modulate the activation of myeloid or epithelial cells, bone marrow derived macrophages (BMMs) or  bone marrow derived dendritic cells (BMDCs) were treated with 100 ng/mL of E.coli LPS and different concentrations of each SCFA. In all cases SCFA modulated surface expression of CD40 in BMDCs (p<0.05). Effects of butyrate and propionate were evident at lower concentrations than lactate and acetate. Butyrate and propionate modulated IL6 generation at concentrations higher than 10 mM (p<0.05), without affecting IL12 production. Lactate modulated IL6, IL1b and IL12 production in BMM, at concentrations higher than 20 mM (p<0.05) which correlated with modulation of the increase in glycolitic rate observed upon TLR4-dependent activation. Flagellin NFkB-mediated activation of intestinal epithelial cells was modulated by all SCFA treatments. Butyrate and propionate showed these effects at concentrations higher than 1 mM whereas lactate and acetate modulated CCL20, CXCL2 and CXCL10 expression at concentrations higher than 10 mM. SCFA can modulate TLR-activated epithelial and myeloid cells at concentrations usually found in large bowel lumen.