Can Fungi Activate your Natural Killer Cells?
- Mar 22
- 4 min read
What are Natural Killer Cells Again...?
Natural Killer (NK) cells are your first line of defense, specialized white blood cells and key components of the innate immune system. They identify and destroy virus-infected cells and early-stage tumors. They literally act as "natural killers" as they destroy cancerous or infected cells by producing cytokines (small signaling proteins). Pretty sweet, right? You're probably thinking "Well, what do a couple of fungi have to do with any of this, then?"
Reishi
Reishi is arguably the most revered fungus in traditional Asian medicine to the point that it's known as the "Mushroom of Immortality". There's so much lore and medicinal uses behind this mushroom that I could make multiple other blog posts, but let's focus on it's role with your immune system for now.
While many immune boosters work indirectly, Reishi water extracts can activate NK cells directly. How? This is achieved through a specific interaction between the mushroom's bioactive compounds, ex., 𝜷-glucans and the receptors on the surface of your NK cells. Reishi polysaccharides (chains of carbohydrates) bind to "activating" receptors on the NK cell surface, which triggers a Mitogen-Activated Protein Kinase (MAPK) signaling pathway. That's basically a fancy (and long!) way to name an internal communication system that tells the cell to transition from a "resting" state to an "active combat" state. This MAPK signal then commands the cell to produce and release Perforin and Granulysin, which are described below.
Perforin: Acts like a metaphorical drill (a really, really, really tiny metaphorical drill!) to puncture holes in the membranes of target cells.
Granulysin: An antimicrobial protein that enters those holes to trigger apoptosis, programmed cell death, in the target cell.
In a 2014 study, researchers observed that Reishi water extracts significantly increased NK cell cytotoxicity (killing power) against various cancers, and in another 2019 study, reishi was shown to increase the total population of NK cells by 1.5 times. On top of that, it made them more lethal: reishi boosted the NK cells' cytotoxicity by 31.7%, and triggered the release of chemical messengers that coordinate immune response.
Turkey Tail
Before we get into the science, I have to point out how much I love the name of this mushroom, which is why I'll be choosing "Turkey Tail" in the poll at the end of this post.
So, what's the deal with this mushroom and NK cells? Well, a study titled "Polysaccharide Krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells" provides some insight on this. Your immune system consists of "sentinel" cells (like macrophages and dendritic cells) patrolling the body. They have sensors on their surface called Toll-Like Receptors (TLRs). These receptors are designed to recognize danger signals such as bacteria, viruses, or tumor cells and trigger an immune response. The active compound in Turkey Tail is Polysaccharide K (PSK), also known as Krestin, which binds to TLRs. Research has found that when PSK binds to the TLR2 receptor, it triggers a strong immune response and increases activity of Natural Killer cells and T-cells, which help the body attack cancer cells or pathogens.
Maitake
Maitake is a medicinal mushroom native to Asia and North America, and, not suprisingly, it has immune-enhancing benefits (after all, if it didn't, it wouldn't be in this blog post!). It actually has two common names: Hen of the Woods and its Japanese common name, Maitake, which is used in this post. By this point, you've probably got the gist of things around here: we'll be looking at another study. This one was published in the Journal of Medicinal Food, where it displayed maitake's antitumor effect in tumor-bearing mice by enhancing the immune system through activation of macrophages, T cells, and NK cells. Maitake D-Fraction, extracted from the mushrom, appears to repress cancer progression and stimulated/increased NK activity in all patients examined. The study also noted that Maitake D-Fraction hindered metastatic progress (the spread of cancer to other parts of the body).
A literature review of studies on Maitake and the immune system notes that specialized protein-sugar molecules found in Maitake (D-fraction, X-fraction, and grilofan) activate your NK cells, macrophages, and cytotoxic T cells simultaneously. Unlike many treatments that only target one area, Maitake coordinates both your innate (fast-acting) and adaptive (specialized) immune responses, forcing your body to produce critical chemical messengers like Interleukin-1 and Interleukin-2 to drive a high-speed defense against invaders. Maitake extracts can also provide significant health benefits for breast, liver, colon, brain, and kidney cancers, all without showing any toxic side effects.
Which of these fungi would you be the most willing to try?
Reishi
Turkey Tail
Maitake
Well, there's the data! I know this one was pretty study heavy, but it's important to validate the claims of fungal immune supplement sellers, and even more so to understand the science behind something you or a loved one might be considering adding to your plate, which is exactly why I make these blog posts! In my opinion, I think that these 3 fungi have quite a bit of potential as adjunctive treatments.
Bibliography
Chang, Chih-Jung et al. “Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin.” Innate immunity vol. 20,3 (2014): 301-11. doi:10.1177/1753425913491789
Sohretoglu, Didem, and Shile Huang. “Ganoderma lucidum Polysaccharides as An Anti-cancer Agent.” Anti-cancer agents in medicinal chemistry vol. 18,5 (2018): 667-674. doi:10.2174/1871520617666171113121246
Lu, Hailing et al. “Polysaccharide krestin is a novel TLR2 agonist that mediates inhibition of tumor growth via stimulation of CD8 T cells and NK cells.” Clinical cancer research : an official journal of the American Association for Cancer Research vol. 17,1 (2011): 67-76. doi:10.1158/1078-0432.CCR-10-1763
Kodama, Noriko et al. “Effect of Maitake (Grifola frondosa) D-Fraction on the activation of NK cells in cancer patients.” Journal of medicinal food vol. 6,4 (2003): 371-7. doi:10.1089/109662003772519949
Camilleri, Emma et al. “Unveiling the full spectrum of maitake mushrooms: A comprehensive review of their medicinal, therapeutic, nutraceutical, and cosmetic potential.” Heliyon vol. 10,9 e30254. 26 Apr. 2024, doi:10.1016/j.heliyon.2024.e30254
