Macrophage activation by edible mushrooms is due to the collaborative interaction of toll-like receptor agonists and dectin-1b activating beta glucans derived from colonizing microorganisms

Authors: ZHANG, JIN - University Of Mississippi; Tyler, Heather; HARON, MONA - University Of Mississippi; JACKSON, COLIN - University Of Mississippi; PASCO, DAVID - University Of Mississippi; PUGH, NIRMAL - University Of Mississippi

Submitted to: Food & Function
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2019
Publication Date: 11/1/2019
Citation: Zhang, J., Tyler, H.L., Haron, M.H., Jackson, C.R., Pasco, D.S., Pugh, N.D. 2019. Macrophage activation by edible mushrooms is due to the collaborative interaction of toll-like receptor agonists and dectin-1b activating beta glucans derived from colonizing microorganisms. Food & Function. 10:8208-8217.

Interpretive Summary: In addition to culinary purposes, mushrooms are also consumed for their medicinal properties. Prior research indicates that cell wall components from bacteria that colonize mushrooms are a major contributor to the immune activity seen in response to water-soluble extracts from several types of mushrooms by stimulating toll-like receptors. This led to the hypothesis that mushrooms may also contain immune enhancing substances derived from other colonizing microorganisms, such as yeasts or molds. Scientists at the University of Mississippi in Oxford and the USDA-ARS Crop Production Systems Research Unit in Stoneville, MS conducted a study to determine if yeasts or molds contribute to immune activation seen in response to water-insoluble mushroom extracts. Insoluble components from medicinal mushrooms (ex. maitake, oyster, shiitake, etc.), but not culinary mushrooms (ex. white button, portobello, etc.), activated an immune response pathway via dectin-1b receptors. This elevated immune response correlated with higher levels of yeast colonization. When assayed together, the soluble and insoluble mushroom extracts had a synergistic interaction, stimulating macrophage cells higher than the theoretical additive effect of each individual extract. The results of this study demonstrate that water-soluble compounds from bacteria and water-insoluble compounds from yeast that colonize medicinal mushrooms both contribute to eliciting an immune response.

Technical Abstract: Research supports the theory that the microbiome of plants and mushrooms produce potent activators of pathogen recognition receptors which are principal contributors to the stimulation of macrophages. We have previously reported that the in vitro macrophage stimulatory activity of water-soluble extracts from 13 different types of edible mushrooms is predominantly due to bacterial components originating from the naturally occurring bacterial communities within these materials. The purpose of the current study was to further investigate the bacterial-dependent activity of the water-soluble extracts and assess whether these 13 types of mushrooms contain water-insoluble beta glucans that activate the dectin-1b signaling pathway. Activity of the water-soluble extracts was predominantly due to Toll-like receptor 2 (TLR2) and TLR4 agonists. For dectin-1b-dependent activity (indicative of water-insoluble beta glucans), culinary mushrooms (Agaricus bisporus varieties) were essentially inactive, whereas most of the medicinal mushrooms (Lentinula edodes, Grifola frondosa, Hypsizygus marmoreus varieties, Flammulina velutipes) exhibited potent activation. A. bisporus samples with no detectable dectin-1b-dependent activity had yeast colony forming units that were 687 times lower than L. edodes exhibiting high activity, indicating that the active insoluble beta glucans are derived from colonizing yeast. We also found that co-stimulation of macrophages with the TLR agonists and insoluble beta glucan results in a synergistic enhancement of in vitro cytokine production. Taken together, these findings indicate that the in vitro macrophage activating potential of edible mushroom is due to the collaborative interaction of water-soluble TLR agonists (derived from colonizing bacteria) and water-insoluble beta glucans (derived from colonizing yeast).