The marine food is named "Blue Food". Compared with terrestrial food, "blue food" can provide higher quality and richer protein, vitamins, unsaturated fatty acids, polysaccharides, dietary fiber and minerals, etc., and some deep-sea extracts have been converted into nutrients and health products/medicines. Polysaccharides are important bioactive macromolecules in marine animals and plants, with anti-aging, anti-inflammatory, antibacterial, antiviral and immunomodulatory functions and other biological activities. The regulation of immune response by polysaccharides is one of the current research hotspots.
Therefore, Gu Fudie, Zhou Yu, Liu Qingmei et al. from Jimei University reviewed the research progress on the immunomodulatory activity of polysaccharides derived from "blue food", mainly expounding the regulatory effect of carbohydrate nutrients in molluscs marine animals and seaweed on natural/adaptive immune cells and immune responses, and focusing on the different applications of pro-inflammatory polysaccharides and anti-inflammatory polysaccharides, as well as their interaction with probiotics in vivo and their role in intestinal microecological balance, in order to provide theoretical support for the research and development of foods based on the immunomodulatory function of polysaccharides derived from "blue food".
1 Introduction to polysaccharides from "blue food" sources
Classification of polysaccharides from "blue food" sources
According to the source, marine polysaccharides can be divided into three categories: marine plant polysaccharides, marine animal polysaccharides and marine microbial polysaccharides. The abundant content of algal polysaccharides in marine plant polysaccharides is an important resource for the drug development of marine polysaccharides. Marine animal polysaccharides include chitosan in crustaceans, chondroitin sulfate in cartilage fish bones, glycosaminoglycans in clams, etc. According to the carbohydrates and other biological macromolecules they bind, marine polysaccharides can be divided into lipopolysaccharides, pure polysaccharides, peptidoglycans and glycoproteins, etc., and the common pure polysaccharides are dextran and glucan; According to the structure of the backbone, it can be divided into linear polysaccharides and branched-chain polysaccharides, and most of the branched-chain polysaccharides have a variety of biological functions including immunomodulatory activities.
Preparation of polysaccharides derived from "blue food".
The preparation methods of polysaccharides derived from "blue food" mainly include water extraction, acid-base treatment, ultrasonic extraction, microwave extraction and enzymatic hydrolysis, as well as mixed extraction. In the preparation process of polysaccharides derived from "blue food", in order to obtain polysaccharides with high purity, further purification is often required, and according to the different properties of polysaccharides, the commonly used separation and purification methods mainly include column chromatography, quaternary ammonium salt precipitation, step-by-step precipitation and membrane separation.
Application of polysaccharides derived from "blue food".
The antibacterial, anticorrosive, protein denaturation, starch aging, fatty acidification, moisturizing and dehydration properties of marine polysaccharides show great potential for their application in the food industry. Compared to chemical additives, marine polysaccharides are safer and healthier and can be used as thickeners, gelling agents and preservatives. Marine polysaccharides also have a wide range of applications in the field of biomedical materials, such as drug delivery, tissue engineering, wound dressings, and sensors.
In summary, polysaccharides in the ocean have a wide range of sources, rich types and broad application prospects. With the deepening of research, it has been found that the good regulatory effect of polysaccharides on the immune system is the key factor for its biological activity and maintenance of health and homeostasis. Due to the rich and diverse subsets of immune cells in the body, they play different roles in different organs, diseases, and stress stimuli, and how polysaccharides regulate immune response under the intervention of complex external and internal factors is an important scientific question in current research.
2. The regulatory effect of polysaccharides derived from "blue food" on innate immune cells
In this paper, we elucidate the innate immune system regulatory activity of polysaccharides derived from "blue food" based on different innate immune cells, such as macrophages, dendritic cells (DCs), and natural killer cells (NK).
Effect of polysaccharides derived from "blue food" on macrophages
Macrophages can directly engulf virus-infected cells or spontaneously cancerous tumor cells, and secrete cytokines, chemokines, etc. to recruit other immune cells, which directly or indirectly act on histiocytes and inflammatory responses. Therefore, targeted regulation of macrophages can well intervene in the occurrence and development of immune responses.
At present, there has been a lot of research on the regulation of macrophage function by polysaccharides derived from "blue food". It was found that the extraction of a sulfate polysaccharide from Triceratophenae could enhance its immunomodulatory activity by improving macrophage viability and upregulating the expression of some cytokines. The polysaccharides in Algae can enhance the viability of macrophages and promote the proliferation of macrophages. Fucoidan sulfate isolated from brown algae and polysaccharide sulfate extracted from cystis can stimulate the release of nitric oxide and inflammatory factors tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 by activating nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, thereby promoting their immune-enhancing ability.
A novel polysaccharide was isolated from the viscera of sea cucumber, which can enhance the phagocytic activity of RAW264.7 cells by activating the Toll-like receptor 4-mediated MAPK and NF-κB signaling pathways. Glycosaminoglycans derived from Pinctada hepu oyster enhanced the phagocytosis of macrophages to neutral red and fluorescein isothiocyanate-labeled E. coli. Glycosaminoglycans derived from Pinctada hepu oyster enhanced the phagocytosis of macrophages to neutral red and fluorescein isothiocyanate-labeled E. coli.
Effect of polysaccharides derived from "blue food" on DCs
DCs are the most abundant antigen-presenting innate immune cells known, and impaired DCs function can seriously impair the normal immune defense process of the host, which is one of the main pathogenesis of a variety of immune dysregulated diseases, and inhibition of DCs activation can treat chronic inflammation and autoimmune diseases.
At present, there are extensive studies on the immunomodulatory effect of polysaccharides derived from "blue food" on DCs. Studies have found that Alveolithophyllum sulfate polysaccharides can induce the upregulation of costimulatory molecules and the production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs), thereby promoting the maturation of DCs. Acantha can directly induce the activation of BDCA1+ and BDCA3+ subsets of human peripheral blood DCs, up-regulate the function of MHC-class I and II, and induce the production of pro-inflammatory factors, thereby enhancing the immune activity of DCs. Fucoidan can stimulate the immune function of DCs and improve the expression of surface markers and heterologous proliferation of DCs after chemotherapy treatment.
Effect of polysaccharides derived from "blue food" on NK cells
NK cells mediate the innate immune response and are key cells of the innate immune system. At present, there are many reports on the regulation of NK cells by carbohydrates derived from marine plants. It was found that the treatment of NK cells with Acanthus polysaccharide found that the expression of CD69 on the surface of NK cells was up-regulated and some cytotoxic substances were produced, indicating that Acantha spinicoida could effectively activate NK cells. The polysaccharide was extracted from Sargassum and confirmed that the polysaccharide could enhance the killing activity of NK cells through target cell release experiments. Glycosaminoglycans were extracted from sea cucumbers, and it was found that they could improve the cytotoxicity and marker enzyme activity of cyclophosphamide-induced immunosuppressed mouse NK cells, which proved that the polysaccharide had a certain degree of recovery effect on the innate immunity of the body.
Innate immune cells are the body's first line of defense against foreign substances or pathogens, and the carbohydrates in a variety of "blue foods" can play a good role in regulating innate immune cells, and their regulatory mechanisms are shown in Table 1.
3. The regulatory effect of polysaccharides derived from "blue food" on adaptive immune cells
The adaptive immune system mainly includes cellular immunity and humoral immunity, which is the third line of defense of the immune system and mainly plays a specific killing role in the body. In cellular immunity, T cells can differentiate into different subsets of cells under different states of immune stress: helper T cells, killer T cells, and regulatory T cells (Tregs). The secretion of cytokines by different cell subsets can lead to the occurrence of related immune diseases or immune escape diseases (such as tumors, allergies, inflammation, viral infections, etc.). Many studies have found that polysaccharides derived from "blue food" have a certain regulatory effect on adaptive immune cells and can inhibit the occurrence of related diseases.
Effect of "blue food" derived polysaccharides on helper T cells
Th1 and Th2 occupy a dominant position in helper T cells in the pro-inflammatory response, and they have different functions and secrete different cytokines. Th1 cells secrete IL-2, IL-12, IFN-γ, TNF-α, etc., and participate in cell-mediated immune responses. Th2 cells secrete IL-4, IL-5, IL-6, IL-10, etc., which promote humoral or allergic reactions.
At present, there have been a lot of studies on the immunomodulatory effect of "blue food" derived polysaccharides on helper T cells. Wakame polysaccharides can activate the immune response of Th1 cytokines IFN-γ and IL-12 in the spleen of mice, inhibit Th2 cytokine levels, and reduce IgE levels. The algal polysaccharides in "blue food" have immunomodulatory effects on helper T cells. The high-pressure degradation method was used to prepare the degraded sulfate polysaccharides of Porphyra tantanensis, and the regulatory effect on Th1 and Th2 cells was enhanced compared with that without degradation.
Effect of polysaccharides derived from "blue food" on cytotoxic T lymphocytes
Cytotoxic T lymphocytes (CTLs) are essential for the removal of foreign substances such as viruses or bacteria and also play a key role in modern personalized cancer immunotherapy. CTLs perform their effector functions primarily through two common killing pathways: the cleavage particle and the Fas/Fas ligand pathway. CTLs and NK cells constitute an important line of defense against virus and tumor immunity.
Current studies suggest that CTLs play a direct or indirect role in immune surveillance and anti-tumor immunity. A novel algae sulfate oligosaccharide MS80 was injected to treat tumor mice, and it was found that the sugar could significantly increase the infiltration of CD8+ T cells, inhibit the primary tumors of mice carrying 4T1, and exert a good anti-tumor effect. The effect of wakame polysaccharides on cyclophosphamide-induced C57BL/6 immunosuppression model mice, and it was found that the proportion of CD8+ T cells in the spleen of mice was significantly increased, and it was determined that wakame polysaccharides could be used as a promising marine natural immunostimulant.
Effect of polysaccharides derived from "blue food" on Treg
Treg can recognize the T cell receptor-antigen peptide presented by the MHC molecule of the target cell and exert a certain immunosuppressive effect. For allergic reactions and some autoimmune diseases, the enhancement of Treg can play a good role in inhibiting the occurrence and development of diseases. As a result, Treg is a target for the treatment of many immune diseases.
The up-regulation rate of oligosaccharides sulfate on Treg was 22.2%~97.1%, and the allergic reaction of mice was alleviated by releasing IL-10 and reducing basophil degranulation. Oligosaccharides of A. chinensis sulfate can promote Treg differentiation and related cytokine secretion, and significantly inhibit the proliferation of effector CD4+ T cells. Effervescent tablets containing red coidan extracted from seaweed and seaweed can increase serum IL-10 and TGF-β levels in mice, and upregulate the amount of CD4+Foxp3+Treg in the spleen, thereby alleviating ovalbumin-induced allergic reactions.
Adaptive immune cells exist in the body's acquired defense system, which is gradually built up after birth, and only acts against a specific pathogen or foreign substance. A variety of "blue food" derived polysaccharides can exert immunomodulatory effects by regulating adaptive immune cells, and their regulatory mechanisms are shown in Table 2.
4. Application of polysaccharides derived from "blue food" in immune homeostasis and immune-related diseases
Due to the different structures and types of polysaccharides, there will be certain differences in their properties, and some studies have shown that some "blue food" derived polysaccharides have the dual effects of enhancing the body's inflammatory response ("pro-inflammatory") and inhibiting the body's inflammation ("anti-inflammatory").
The role of pro-inflammatory "blue food" derived polysaccharides in antitumor and immune adjuvants
Studies have found that polysaccharides derived from "blue food" can promote the activation of macrophages, DCs antigen presentation and other natural immune cells, thereby exerting a certain immunomodulatory effect on the body, and by promoting tumor cell apoptosis and inhibiting the growth cycle of tumor cells, so as to achieve the purpose of anti-tumor. The study also found that polysaccharides derived from "blue food" can promote the maturation of DCs, which can be used as adjuvants in the treatment of diseases, and has great potential in the research and development of anti-tumor adjuvant drugs.
At present, most studies have used polysaccharides and tumor cells to co-culture in vitro to verify the tumor growth inhibition ability of polysaccharides. Polysaccharides can also inhibit the growth of tumors by enhancing the body's immune function, and abalone visceral and muscle polysaccharides can inhibit tumor cell proliferation and survival through immune-enhancing effects.
The role of anti-inflammatory "blue food" derived polysaccharides in the regulation of autoimmune diseases and inflammation
The occurrence of autoimmune diseases is mainly caused by the dysfunction of the autoimmune system, which attacks its own tissues and organs, and often has multi-target immune activation, so it cannot be treated with a single drug. As a special food ingredient, anti-inflammatory active polysaccharides derived from "blue food" provide a good defense strategy for the regulation of autoimmune diseases and inflammation.
The regulatory effect of polysaccharides derived from "blue food" on immune cells can be intuitively reflected in the control of diseases, and the regulatory mechanism is shown in Table 3.
Effect of polysaccharides derived from "blue food" on the body's intestinal microbiota-immune balance
The intestinal flora plays a very important role in the maintenance of human health, nutrient metabolism and immune homeostasis. A large number of studies have proved that polysaccharides derived from "blue food" can improve intestinal health by regulating the microecological balance of intestinal flora, which plays an important role in ensuring human health and preventing diseases.
Figure 1 summarizes the mechanism of action of "blue food" derived polysaccharides in regulating the differentiation and function of innate immune cells such as macrophages, DCs, and NK cells, as well as adaptive immune cells such as helper T cells, CTLs, and Tregs.
5 Conclusion
Polysaccharides in the ocean are abundant active substance resources and have the potential for development and utilization. At present, the biological function of polysaccharides derived from "blue food" has been verified by many experiments, and it has the functions of immunosuppressive activity, regulation of immune homeostasis, etc., and can regulate the differentiation and function of natural immune cells such as macrophages, DCs, NK cells, and adaptive immune cells such as helper T cells, CTLs, and Tregs. The main reasons are:
1) Most of the reports are limited to studying the effects of "blue food" derived polysaccharides on immune cell subsets, and how to regulate the activation and differentiation of immune cells and the specific mechanisms are not well studied;
2) although the positive effects of polysaccharides in "blue foods" in immunomodulation are understood, their cytotoxic effects in immune homeostasis and other organ homeostasis remain unclear;
3) Many studies on the regulation of immune response by polysaccharides mainly rely on immunology-related cell lines, but the cell lines with infinite passage can maintain some immunological characteristics, but more of them show the characteristics of cancer cells, so the use of polysaccharides to evaluate the immunomodulatory effect of "blue food" derived polysaccharides has clear limitations.
Therefore, future research should pay more attention to the role of "blue food" derived polysaccharides in targeting immune cells and their interaction between regulating intestinal microecology and immune cells, so as to enrich and improve the knowledge system of the regulatory effect of marine polysaccharides on the immune system, so as to develop functional foods or foods for special medical purposes based on polysaccharides derived from "blue food" for tumors and autoimmune diseases that are difficult to solve in clinical practice, as well as direct intake of nutritional components that regulate the body's immune system in the diet, so as to promote " High-value utilization of "blue food".
This article "Research Progress on the Immunomodulatory Activity of Polysaccharides Derived from "Blue Food" is from Food Science, Vol. 44, No. 13, pp. 272-280, 2023.