Polysaccharides, Mushrooms & The Complement Immune System

The medicinal properties of fungi are well established. The primary immune-activating constituents include various polysaccharides, including beta glucans, mannans and lectins. The effects of these polysaccharides have far-reaching possibilities for various aspects of the human immune system, including those relating to innate, complement immunity.

Polysaccharides & The Complement Immune System

The complement immune system is a key part of the ancient, innate immune response. The innate immune system is believed to evolutionarily pre-date the adaptive immune system. The complement immune response consists of 3 pathways: the lectin pathway, the alternative pathway and the classical pathway. The complement system consists of a series of cleavage reactions, whereby complement proteins are split off into fragments, and in certain steps bond to other complement fractions. The result of classical and alternative pathway activation results in the elimination of pathogens, called opsonization.

Unlike the classical and alternative pathways, the lectin pathway does not use or recognize an antibody. Instead, the lectin pathway can use polysaccharides, ficolin, collectin or mannose binding lectin (MBL) to create adhesive bonds in order to bind pathogens.

The primary immune constituents of the lectin pathway are complements C4 and C2. Integral to their actions, and the actions of MBL are protease enzymes, MASP-1 and MASP-2 (mannan-binding lectin serine proteases 1 and 2). MASP-1 cleaves complement C4 and C2 into C4b2a. MASP-1 is also involved in coagulation reactions, specifically in the cleavage of fibrinogen into fibrin, as well as the cleavage of Factor VIII. MASP-2 cleaves complement C4 into C4a and C4b, and Complement C2 into C2a and C2b, respectively.

A substantial amount of clinical research among CIRS practitioners (chronic inflammatory response syndrome) finds that individuals with chronic inflammation have elevations in C4a. Both mold exposure and Lyme disease are associated with higher C4a levels (R). CFS/ME is associated with higher C4a levels (R). The significance of an elevation of C4a in these conditions is associated with activation of the lectin pathway of the complement immune system, the involvement of MASP-1, MASP-2, and MBL.

It has been demonstrated that the lectin pathway is integral in the protection from opportunistic fungi such as candida, as well as certain bacteria and viruses (R). The activation of MBL is necessary for the completion of lectin activation and pathogenic removal, as well as the recruitment of the adaptive immune responders, T and B-cell lymphocytes.

Deficiencies of C4 and C2 are etiological in various diseases, including autoimmune conditions, lupus, type 1 diabetes, inflammatory bowel diseases, vasculitis, rheumatoid arthritis, and greater risk of infection. Deficiency of MBL leads to immune deficiency and opportunistic infections, and the development of upper respiratory infections, pneumonia as well as meningitis (R).

Among the myriad immune-modulatory effects of 1,3 beta glucans, they have shown to activate the lectin pathway (R). This research may be significant for individuals dealing with suspected lectin pathway activation, such as in Lyme disease, mold, CIRS and CFS/ME.

Constituents of the reishi mushroom have been found to activate the alternative and classical complement pathways (R).

While research has not yet demonstrated its specific complement effects, a mushroom hericium erinaceus, aka Lion’s mane possesses one of the highest polysaccharide concentrations. Research has found Lion’s Mane is capable of inhibiting reverse transcriptase of HIV retrovirus (R), as well as increasing the expression of the antioxidant genes Nrf2 and gamma glutamyl cysteine (which activates glutathione directly) (R). Lion’s mane also has neuroprotective and neurotrophic effects, by acting to increase NGF (nerve growth factor) (R). Does lion’s mane activate the complement immune system? I personally believe future research will confirm this.

Questions remain: 

• Can mannan polysaccharides modulate through the lectin pathway?
• What role if any do other polysaccharides play in the complement immune system?
• Do polysaccharides modulate through the coagulation system? Preliminary clinical evidence suggests that certain types of supplemental polysaccharides may affect heparin sulfate, a glycosaminoglycan comprised of polysaccharides. Heparin sulfate is involved in extracellular matrix functions, including those related to anti-coagulation.