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Role of intestinal epithelial cells and involvement of TLRs in immune effects of AHCC (638.4)

Active Hexose Correlated Compound (AHCC®) is a fermented mushroom extract that is commercially available and promoted for immune support. Available data suggest that AHCC supplementation clearly affects immune outcomes and immune cell populations, endowing it with potent anti‐inflammatory effects. The mechanism by which AHCC exert its anti‐inflammatory effects is not well understood yet. The present work aimed to analyze the immunomodulatory activity of AHCC in the gut, and to study the role of Intestinal Epithelial Cells (IECs) in AHCC and TLRs signaling. BALC/c mice were fed AHCC by gavage. Immunomodulatory activities were assessed by cytokines production and immunohistochemistry analyzes as well as monitoring of IgA levels. AHCC effects on ex vivo primary cell cultures from IECs were examined after challenges with LPS and E.coli, along with its effects on both TLR‐2 and TLR4. The results showed that the presence of SIgA in the intestinal fluid was significantly higher in AHCC fed mice than in the control group. Cytokines analysis also showed a significant increase in IL‐10 and IFNγ in AHCC fed mice. In ex vivo cell cultures of IECs, AHCC did slightly increase IL‐6 production when compared to the control. This physiological increase and magnitude in IL‐6 by AHCC differs from the inflammatory response of IECs to LPS and E.coli. In TRLs blocking experiments, TLR‐2 and TLR‐4 are confirmed to play major role in AHCC priming effects on IECs. We concluded that AHCC may play a crucial role on the orchestration of immune response by priming the immune response through TLR2 and TLR‐4 gate in the IECs and by the maintenance of homeostasis at the gut.