- Polysaccharides are among the most extensively studied natural biomolecules with immunomodulatory and immunostimulant activities, owing to their structural diversity, biocompatibility, and biological relevance. Found in plants, fungi, algae, bacteria, and animals, these long-chain carbohydrates can interact with the immune system directly or indirectly, influencing both innate and adaptive immunity. Their biological effects are largely determined by structural features such as monosaccharide composition, glycosidic linkages, degree of branching, molecular weight, and functional modifications (e.g., sulfation, acetylation).
- One of the most important immunostimulant polysaccharides is β-glucan, widely found in fungi, yeast, and cereals. β-glucans are recognized by pattern recognition receptors (PRRs) such as dectin-1, complement receptor 3 (CR3), and Toll-like receptors (TLRs) on immune cells. This recognition stimulates macrophages, dendritic cells, natural killer (NK) cells, and neutrophils, leading to enhanced phagocytosis, cytokine release (e.g., TNF-α, IL-6, IL-12), and improved antigen presentation. Consequently, β-glucans act as biological response modifiers, boosting host defense against infections and cancers.
- Marine-derived polysaccharides, such as fucoidan and laminarin from brown algae, also demonstrate potent immunomodulatory properties. Fucoidan, a sulfated polysaccharide, can activate macrophages, promote lymphocyte proliferation, and modulate complement activity. Its sulfation pattern enhances interactions with immune receptors, enabling it to regulate both pro-inflammatory and anti-inflammatory pathways. Laminarin, while less potent than fucoidan, supports immune stimulation and complements the anticancer and antioxidant effects of marine polysaccharides.
- Plant polysaccharides like arabinogalactans and pectins exhibit immunomodulatory effects primarily through interactions with gut-associated lymphoid tissue (GALT). They serve as prebiotics, altering gut microbiota composition and enhancing the production of short-chain fatty acids (SCFAs), which in turn regulate immune responses and inflammatory pathways. Arabinogalactans, for example, have been shown to increase NK cell activity and improve resistance against respiratory infections.
- Microbial polysaccharides, including peptidoglycan from bacterial cell walls and capsular polysaccharides from pathogenic bacteria, are recognized as pathogen-associated molecular patterns (PAMPs). These molecules stimulate immune surveillance by binding to TLRs and NOD-like receptors (NLRs), triggering innate immune responses. While some bacterial polysaccharides act as virulence factors to evade immunity, many are used in vaccine development (e.g., pneumococcal and meningococcal polysaccharide vaccines), where they elicit strong protective antibody responses.
- Another key class, fungal polysaccharides, especially scleroglucans and lentinans, have been investigated for their immunomodulatory potential. Lentinan, a β-glucan extracted from Lentinula edodes (shiitake mushroom), is clinically used as an immunotherapeutic adjuvant in cancer treatment. It enhances T-cell activation and promotes the production of interleukins, complementing chemotherapy by boosting the host immune system.
- At a mechanistic level, polysaccharides can exert dual immunomodulatory effects. They may stimulate immune activity in immunocompromised conditions, such as infections or cancer, while also suppressing excessive immune responses in cases of chronic inflammation or autoimmune disorders. This balance arises from their ability to influence cytokine production, regulate immune cell proliferation, and modulate oxidative stress. For example, some polysaccharides enhance Th1-mediated cellular immunity, while others promote regulatory T-cell (Treg) responses, helping to maintain immune homeostasis.
