Negative Regulation of Innate Immune Signaling by Components of the Button Mushroom Agaricus bisporus

Scope: Mushrooms are valued as an edible and medical resource for millennia. As macrofungi, they possess conserved molecular components recognized by innate immune cells like macrophages, yet unlike pathogenic fungi, they do not trigger the immune system in the same way. That these well-tolerated foods both avoid immuno-surveillance and have positive health benefits, highlights the dearth of information on the interactions of mushroom-derived products with the immune system. Methods and results: Using powders produced from the common white button mushroom, Agaricus bisporus, it is observed that pre-treatment of mouse and human macrophages with mushroom powders attenuates innate immune signaling triggered by microbial ligands like LPS and beta-glucans, including NF kappa B activation and pro-inflammatory cytokine production. This effect of mushroom powders is observed at lower doses of TLR ligands, suggesting a model of competitive inhibition whereby mushroom compounds bind and occupy innate immune receptors, precluding activation by microbial stimuli. This effect is preserved following simulated digestion of the powders. Moreover, in vivo delivery of mushroom powders attenuates the development of colitis in a DSS-mouse model. Conclusion: This data highlights an important anti-inflammatory role for powdered A. bisporus mushrooms, which can be further utilized to develop complementary approaches to modulate chronic inflammation and disease.