Resistant starches differentially stimulate Toll-like receptors and attenuate proinflammatory cytokines in dendritic cells by modulation of intestinal epithelial cells

Scope: Main objectives of this study were (1) to demonstrate direct signaling of starch on human dendritic cells (DCs), (2) to study whether this is mediated by the pattern recognition receptors such as Toll-like receptors (TLRs) and (3) to study whether intestinal epithelial cells (IECs) are involved in modulating the starch induced immune activation of DCs. Methods and results: Two different types of resistant starch, High-maize (R) 260 (RS2) and Novelose (R) 330 (RS3) were characterized for their starch content and particle size. Human DCs and reporter cells for TLRs were incubated with starches and analyzed for NF-kB/AP-1 activation. Complex coculture systems were applied to study the cross-talk. High-maize (R) 260 predominantly binds to TLR2 while Novelose (R) 330 binds to TLR2 and TLR5. The strong immune-stimulating effects of High-maize (R) 260 were attenuated by starch-exposed IECs illustrating the regulatory function of IECs. Despite these attenuating effects, DCs kept producing Th1 cytokines. Conclusion: Resistant starch possesses direct signaling capacity on human DCs in a starch-type-dependent manner. IECs regulate these responses. High-maize (R) 260 skews toward a more regulatory phenotype in coculture systems of DCs, IEC, and T cells.