Immune Benefits From Mushroom Consumption

A non-therapeutic study is described. This is an intervention study at two levels of mushroom intake. The number of subjects and experimental assays are selected as a pilot study to generate the dose level and the efficacy. Subjects age 21 to 50 will be recruited and provide a baseline blood draw. The mushroom supplementation will occur for 4 weeks at two levels 85 g (3 ounces) and 170 g (6 ounces). Immunity changes fairly rapidly; in and early study the investigators saw changes in as little as 3 days. Blood is taken again at 4 weeks. Peripheral blood mononuclear cells are isolated from the blood and used freshly isolated, or cultured in autologous serum for 24 hours or for 10 days. Freshly isolated cells will be used to count γδ T cell and NK cells baseline values. After 24 hours of stimulation with a broad based mitogen, culture medium is harvested and assayed for cytokines secreted into the culture medium as well as NK cell activation and proliferation. Finally, cells are harvested after 10 days and assayed for γδ T cell activation and proliferation.

Consumers will benefit from knowing that health benefits can be derived from mushrooms. Potentially, this will stimulate mushroom sales and increase the variety of mushrooms consumed.

γδ T cells reside in epithelial linings of the lung, gut and reproductive tract and although their number is not precisely known, they are in much greater numbers than the circulating αβ T cells. γδ T cells are not activated in the same way as the αβ cells, they are activated more like cells of the innate immune system, by recognition of pathogen-associated molecular patterns (1,2). Recognition of pathogen-associated molecular patterns is rather non-specific, but very effective. For example, prenyl phosphate is a molecule having a pattern that is recognized by receptors of the γδ T cells. Interaction of prenyl phosphate with the γδ T cell receptor results in γδ T cell proliferation; expression of cell surface activation markers, such as cytokine receptors; and lastly, synthesis and secretion of cytokines necessary for communicating with other branches of the immune system. The investigators hypothesize that consuming mushrooms will result in greater proliferation when stimulated and will also enhance their capacity for activation, defined here as cytokine secretion and cell surface marker expression.

A second quality of γδ T cells is their ability to turn off the immune response once it is no longer needed. Carding and Egan (3,4) showed that γδ T cells were responsible for killing activated macrophages after the pathogen had been eliminated. Knockout mouse models show that the elimination of γδ cells promote chronic inflammation, prevent wound healing (5) and may increase the risk for cancer (6,7). The magnitude and the importance of the γδ T cell are just being realized. By strengthening γδ T cells, the investigators will fight pathogen better and resolve inflammation quicker.

It is our hypothesis that there are certain bioactive components that resemble pathogen-associated molecular patterns and interact weakly with the epithelial γδ T cells in such a way that they are "primed", but not activated. The bioactive food components do not interact with the cells with enough strength to cause an actual response, but, later, when the cells do encounter pathogen, they can react quicker and with more intensity if they have already been primed. The primary bioactive components in mushrooms that may interact with immune cells are polysaccharides and glycoproteins and the two major types of mushroom polysaccharides include glucans (both β and α) and heteroglycans. Additionally, mushrooms contain another important polysaccharide, chitin. Chitin is composed of N-acetyl-d-glucosamine units (8,9). These compounds are some likely candidates, in addition to other immuno-modulating compounds such as Vitamin D (10) and B vitamins.