Spiky titanium dioxide nanoparticles-loaded Plantaginis Semen polysaccharide as an adjuvant to enhance immune responses.

The purpose of this study was to prepare spiky titanium dioxide nanoparticles-loaded Plantaginis Semen polysaccharide (SN-TiO2-PSP), and the structural characterization and immune response of infectious laryngotracheitis (ILT) vaccine in Hetian chickens were investigated. The structural characterization of SN-TiO2-PSP was analyzed by FT-IR, TEM, and TGA analysis. And the immune organs indexes, lymphocytes proliferation, specific antibody levels, and ratios of CD4+ and CD8+ T lymphocytes were studied. Structural characterization results showed that SN-TiO2-PSP has a typical polysaccharide absorption peak and good stability. The SN-TiO2-PSP's shape was similar to sea urchin, and its zeta potential and particle size were 27.56 mV and 976.11 nm, respectively. In vivo results showed that SN-TiO2-PSP could enhance the proliferation of peripheral lymphocytes, specific antibody levels, CD4+ and CD8+ T lymphocytes ratios, IL-4 and INF-γ levels in Hetian chickens vaccinated with ILT vaccine on D7, D14, D21, and D28. In addition, SN-TiO2-PSP not only enhanced the indexes of immune organs but also promoted the development of immune organs. Therefore, SN-TiO2-PSP has immune adjuvant activity and may become a new potential immune adjuvant.

Preparation of Amomum longiligulare polysaccharides 1- PLGA nanoparticle and its immune enhancement ability on RAW264.7 cells.

Amomum longiligulare polysaccharides 1 (ALP1) was a glucosan that possessed an immune enhancement ability. However, disadvantages including short biological half-life hindered the application of ALP1. To solve these shortcomings, ALP1 was successfully prepared to nanoparticles (ALPP) with poly (lactic-co-glycolic acid) in the present study. And the optimal preparation conditions were developed by using the response surface method with a Box-Behnken design. The results showed that the encapsulation efficiency of ALPP reached a high level (79.88%) when the volume ratio of the water phase to the organic phase was 1:7, the volume ratio of the primary emulsion to the external water phase was 1:7, and the concentration of F68 was 0.7%. ALPP showed a controlled and sustained release. Meanwhile, the scanning electron microscope results showed that ALPP was a kind of nanoparticles with a diameter of 389.77 nm. In addition, the activating effect of ALPP on macrophages was studied. The results indicated that ALPP showed a better activity on promoting the RAW264.7 cells' activities and polarizing RAW264.7 cells into both M1 type and M2 type macrophages, compared to ALP1.

Characterizations of glucose-rich polysaccharides from Amomum longiligulare T.L. Wu fruits and their effects on immunogenicities of infectious bursal disease virus VP2 protein.

The aim of this study is to explore the characterization of Amomum longiligulare T.L. Wu fruits polysaccharide (ALP) and their immune enhancement effects. Two homogeneous polysaccharides (ALP1 and ALP2) were isolated from the fruits. The structural characterization results showed that ALP1 (26.10 kDa) and ALP2 (64.10 kDa) were both mainly composed of glucose. Furthermore, ALP1 was consisted of (1,2)-α-D-Glcp, (1,2,3)-α-D-Glcp and T-α-D-Glcp, while ALP2 was consisted of T-α-D-Glcp, (1,3)-α-D-Glcp and (1,3,6)-α-D-Glcp. Afterwards, the immune enhancement effects of two polysaccharides were evaluated by determining their effects on immunogenicities of infectious bursal disease virus (IBDV) VP2 protein. Chickens were immunized with IBDV VP2 protein accompanied with ALP1/ALP2. And the results indicated both ALP1 and ALP2 promoted the weights and bursa of fabricius indexes of chickens. In addition, both two polysaccharides increased specific IBDV antibody levels, while ALP1 possessed higher immune enhancement ability and was expected to be an adjuvant for IBDV VP2 protein.

Activation of chicken gamma-delta T lymphocytes by a purified ulvan extract.

Chicken γδ T lymphocytes are present in a variety of tissues such as blood, spleen and intestine. They constitute a major cytotoxic population. In chicken, Salmonella immunization as well as vaccination against Newcastle disease virus are accompanied by an increase of γδ T lymphocytes in peripheral blood, which may be activated, and thus represent a protective immune response. It has been published that activation of avian γδ T cells can occur in a MHC non-restricted manner. Ulvans are complex sulfated polysaccharides composed of disaccharide repetitions found in the cell walls of green algae belonging to the genus Ulva. We recently demonstrated that a purified ulvan extract activates chicken heterophils and monocytes in vivo through TLR2 and TLR4 receptors when given in drinking water. We demonstrate here, that the same extract given once in drinking water at 25 and 50 mg/l, results in increased membrane expression of Major Histocompatibility Complex class 2 as soon as day 2, as detected using flow cytometry. We conclude chicken γδ T lymphocytes to be activated, or at least primed, in vivo, with the extract. Further experiments are required to fully understand whether their activation or priming is the result of direct and/or indirect mechanisms.

Portulaca oleracea L. polysaccharides enhance the immune efficacy of dendritic cell vaccine for breast cancer.

Previous studies have reported that Portulaca oleracea L. polysaccharides (POL-P3b) is an immunoregulatory agent. However, few studies exist on POL-P3b as a novel immune adjuvant in combination with the DC vaccine for breast cancer treatment. In this work, a DC vaccine loaded with mouse 4T1 tumor cell antigen was prepared to evaluate the properties of POL-P3b in inducing the maturation and function of DC derived from mouse bone marrow, and then to investigate the effect of the DC vaccine combined with POL-P3b on breast cancer in vivo and in vitro. Morphological changes of DC were observed using scanning electron microscopy. Phenotypic and functional analyses of DC were detected by flow cytometry and allogeneic lymphocyte reaction. Cytokine levels in the DC culture supernatant were detected by ELISA. Western blotting analysis was used for the protein expression of TLR4, MyD88 and NF-κB. Apoptosis detection and protein expression of the tumor tissue were analyzed by TUNEL staining and immunohistochemistry, respectively. The security of POL-P3b was evaluated by the detection of hematological and blood biochemical indicators and pathological analysis for tissues. POL-P3b can induce DC activation and maturation, which is attributed to increasing the specific anti-tumor immune response, and the mechanism of action involved in the TLR4/MyD88/NF-κB signaling pathway. Experimental results in vivo further suggested that the administration of POL-P3b-treated antigen-primed DC achieved remarkable tumor growth inhibition through inducing apoptosis and enhancing immune responses. Moreover, the POL-P3b-treated DC vaccine was able to inhibit lung metastases. The results proved the feasibility of POL-P3b as an edible adjuvant of the DC vaccine for anti-breast cancer therapy.

A review on antiviral and immunomodulatory polysaccharides from Indian medicinal plants, which may be beneficial to COVID-19 infected patients.

The emergence of the novel coronavirus, SARS-CoV-2 has pushed forward the world to experience the first pandemic of this century. Any specific drug against this RNA virus is yet to be discovered and presently, the COVID-19 infected patients are being treated symptomatically. During the last few decades, a number of polysaccharides with potential biological activities have been invented from Indian medicinal plants. Many polysaccharides, such as sulfated xylomannan, xylan, pectins, fucoidans, glucans, glucoarabinan, and arabinoxylan from Indian medicinal plants, have been shown to exhibit antiviral and immunomodulating activities. Plant polysaccharides exhibit antiviral activities through interference with the viral life cycle and inhibition of attachment of virus to host cell. Intake of certain immune stimulating plant polysaccharides may also protect from the virus to a certain extent. In process of continuous search for most potent drug, Indian plant polysaccharides may emerge as significant biomaterial to combat COVID-19. This review explores a number of polysaccharides from Indian medicinal plants which showed antiviral and immunomodulating activities. It is aimed to provide an overview about the composition, molecular mass, branching configuration and related bioactivities of polysaccharides which is crucial for their classification as possible drug to induce immune response in viral diseases.

Immunostimulatory effects of the intracellular polysaccharides isolated from liquid culture of Ophiocordyceps sinensis (Ascomycetes) on RAW264.7 cells via the MAPK and PI3K/Akt signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese Cordyceps (DongChong XiaCao), a parasitic complex of a fungus Ophiocordyceps sinensis and a caterpillar, is a traditional Chinese medicine. Polysaccharides extracted from O. sinensis have immunomodulatory effects on macrophages. However, the mechanism of polysaccharides on macrophage and the composition of polysaccharides are not known. AIM OF STUDY: We aimed to investigate composition and structure of the intracellular polysaccharides from O. sinensis mycelia (designed as OSP), and evaluate its the immunomodulatory effect on macrophages and its underlying mechanism. MATERIALS AND METHODS: We performed a liquid-state fermentation of O. sinensis to produce mycelia. The DEAE-Sephadex-A25 cellulose column and Sephadex-G100 gel column chromatography were employed to purify and character the intracellular OSP. Macrophages RAW264.7 cells were employed to evaluate OSP's immunomodulatory activity and the possible mechanism responsible for the activation of macrophages in vitro. RESULTS: The average molecular weight of OSP was distributed at 27,972 Da, OSP was composed of xylose, mannose, glucose, and galactose with the ratio of 2.9 : 6.6 : 166 : 2.6, with a trace amount of fucose, arabinose and rhamnose. The phagocytosis of RAW264.7 cells was improved significantly and remarkable changes were observed in the morphology with OSP-treated cells. Real-time quantitative polymerase chain reaction (RT-qPCR) analysis demonstrated that OSP had an ability to regulate the mRNA expression of pro-inflammatory and anti-inflammatory cytokines, and to induce the mRNA expression level of iNOS in a concentration dependent manner in RAW264.7 cells. Western blotting analysis showed that the regulation of NO and cytokines was mediated through mitogen-activated protein kinase (MAPK) and PI3K/Akt signaling pathways. CONCLUSION: This study demonstrated that OSP was with a capacity to activate macrophage cells RAW264.7 for an improvement of immunomodulation activities, which was through regulation of inflammatory mediators via MAPK and PI3K/Akt signaling pathways.

A purified acidic polysaccharide from Sarcandra glabra as vaccine adjuvant to enhance anti-tumor effect of cancer vaccine.

Immunological adjuvants are an important part of tumor vaccines and are critical for stimulating anti-tumor immune responses. However, the clinical needs of strong adjuvants have not been met. In this work, we found that the purified acidic polysaccharide from Sarcandra glabra, named p-SGP, is an ideal adjuvant for tumor vaccines. Cancer vaccines could induce stronger humoral and cellular immune responses when they are adjuvanted with p-SGP. Compared with CpG, a well-studied adjuvant, p-SGP significantly augmented the anti-tumor immunity of various cancer vaccines, which is leading to noticeable inhibition of tumor growth and metastasis in tumor-bearing mice. Moreover, p-SGP promoted dendritic cells (DCs) maturation and Th1-polarized immune response. Toll-like receptor 4 (TLR4) inhibitor TAK-242 could significantly inhibit the expression of mature molecules on the surface of DCs stimulated by p-SGP, suggesting that p-SGP could play the role of activating DCs through the TLR4 receptor. Results of RNA-seq showed that the Delta-like ligand 4 (DLL4) gene in the pathway Th1 and Th2 cell differentiation was significantly up-regulated in the DCs treated with p-SGP, suggesting that p-SGP has a unique mechanism of enhancing anti-tumor immunity.

Mulberry leaf polysaccharide supplementation contributes to enhancing the respiratory mucosal barrier immune response in Newcastle disease virus-vaccinated chicks.

Despite high global vaccination coverage, Newcastle disease (ND) remains a constant threat to poultry producers owing to low antibody levels. Given the respiratory mucosa is the important site for Newcastle disease virus (NDV) vaccination, enhancing respiratory mucosal immunity may help control ND. Our previous study showed that mulberry leaf polysaccharide (MLP) is very promising in delivering a robust balanced immune response, but the effects of it on respiratory immunity in chicks are unknown. In this study, we evaluated the potential of MLP to activate respiratory mucosal immunity and revealed the possible mechanism of MLP as an immunopotentiator for ND vaccines. Chicks were randomly divided into 5 groups: blank control, vaccination control (VC), and low-, middle-, and high-dose MLP (MLP-L, MLP-M, and MLP-H) (n = 30). The serum results of humoral and cell-mediated immune responses showed significant increases in NDV hemagglutination inhibition antibody titer, IgG and IgA antibody levels, and the T-lymphocyte population in the MLP-M group compared with the VC group. Validation of results also indicated remarkable increases in tracheal antibody-mediated immunity and a mucosal immune response in the MLP-M group. Furthermore, the upregulation of TLR7 revealed a possible mechanism. Our findings provided evidence to consider MLP as a potential mucosal vaccine adjuvant candidate against ND in chickens.

Effects of Pinus massoniana pollen polysaccharides on intestinal microenvironment and colitis in mice.

The stability of the intestinal microenvironment is the basis for maintaining the normal physiological activities of the intestine. On the contrary, disordered dynamic processes lead to chronic inflammation and disease pathology. Pinus massoniana pollen polysaccharide (PPPS), isolated from Taishan Pinus massoniana pollen, has been reported with extensive biological activities, including immune regulation. However, the role of PPPS in the intestinal microenvironment and intestinal diseases is still unknown. In this work, we initiated our investigation by using 16S rRNA high-throughput sequencing technology to assess the effect of PPPS on gut microbiota in mice. The result showed that PPPS regulated the composition of gut microbiota in mice and increased the proportion of probiotics. Subsequently, we established immunosuppressive mice using cyclophosphamide (CTX) and found that PPPS regulated the immunosuppressive state of lymphocytes in Peyer's patches (PPs). Moreover, PPPS also regulated systemic immunity by acting on intestinal PPs. PPPS alleviated lipopolysaccharide (LPS) -induced Caco2 cell damage, indicating that PPPS has the ability to reduce the damage and effectively improve the barrier dysfunction in Caco2 cells. In addition, PPPS alleviated colonic injury and relieved colitis symptoms in dextran sodium sulfate (DSS)-induced colitis mice. Overall, our findings indicate that PPPS shows a practical regulatory effect in the intestinal microenvironment, which provides an essential theoretical basis for us to develop the potential application value of PPPS further.

Annona muricata L.-Derived Polysaccharides as a Potential Adjuvant to a Dendritic Cell-Based Vaccine in a Thymoma-Bearing Model.

Dendritic cells (DCs) are powerful antigen-presenting cells that are often used to evaluate adjuvants, particularly for adjuvant selection for various vaccines. Here, polysaccharides (named ALP) isolated from leaves of Annona muricata L., which are used in traditional medicine such as for bacterial infections and inflammatory diseases, were evaluated as an adjuvant candidate that can induce anti-tumor activity. We first confirmed the phenotypic (surface molecules, cytokines, antigen uptake, and antigen-presenting ability) and functional alterations (T cell proliferation/activation) of DCs in vitro. We also confirmed the adjuvant effect by evaluating anti-tumor activity and immunity using an ALP-treated DC-immunized mouse model. ALP functionally induced DC maturation by up-regulating the secretion of Th1-polarizing pro-inflammatory cytokines, the expression of surface molecules, and antigen-presenting ability. ALP triggered DC maturation, which is dependent on the activation of the MAPK and NF-κB signaling pathways. ALP-activated DCs showed an ample capacity to differentiate naive T cells to Th1 and activated CD8+ T cells effectively. The systemic administration of DCs that pulse ALP and ovalbumin peptides strongly increased cytotoxic T lymphocyte (CTL) activity (by 9.5% compared to that in the control vaccine groups), the generation of CD107a-producing multifunctional T cells, and Th1-mediated humoral immunity, and caused a significant reduction (increased protection by 29% over that in control vaccine groups) in tumor growth. ALP, which triggers the Th1 and CTL response, provides a basis for a new adjuvant for various vaccines.

Extraction, structural characterization, and immunoregulatory effect of a polysaccharide fraction from Radix Aconiti Lateralis Preparata (Fuzi).

A water-soluble polysaccharide fraction named FZPS-1 was obtained from Radix Aconiti Lateralis Preparata (Fuzi in Chinese). Physicochemical and instrumental analyses indicated that the purified FZPS-1 with an average molecular weight of 6.29 × 106 Da was composed of D-arabinose and d-glucose with a molar ratio of 7.5:92.5. It would contain the main chain fragments of →4)-α-D-Glc-(1 â†’ 4)-α-D-Glc-(1→, with the side chain of terminal α-L-Ara-(1 â†’ linked at C6 of D-Glc skeleton. FZPS-1 exhibited significant antioxidative activity and immunomodulatory activity, wherein it promotes macrophage phagocytosis and increases the secretion of macrophage-derived biological factors in RAW 264.7 cells, and a cyclophosphamide-induced immunosuppressed model in a dose-dependent manner. Oral administration of FZPS-1 ameliorated chronic diarrhea in rhubarb-induced spleen deficiency rats and was related to its immunomodulatory activity. Therefore, the obtained FZPS-1 could be potentially utilized as a natural immunomodulatory agent in functional food supplements or drugs.

Polysaccharides from Hedyotis diffusa enhance the antitumor activities of cytokine-induced killer cells.

Hedyotis diffusa is a well-known traditional Chinese herbal medicine. The polysaccharides extracted from H. diffusa (HDP) exhibit a range of pharmacological activities. Transfusion of cytokine-induced killer (CIK) cell is one type of adoptive cellular immunotherapy, which is becoming an important method of cancer immunotherapy. In this present study, we investigate the immunostimulatory effect of HDP on CIK cells. CIK cells were generated by culturing and stimulating peripheral blood monocytes of healthy volunteers. They were treated with HDP at three different concentrations (10, 50, and 100 µg/mL). The effect of HDP on CIK cell populations, intracellular cytokine production, and apoptosis was examined by flow cytometry. The antitumor effect of HDP on CIK cells was determined by cytotoxicity assay. Furthermore, the effect of HDP on the antitumor activity of CIK cells in a mouse model was investigated. HDP increased the percentage of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ CIK cells. The HDP-treated CIK cells showed a greater ability to kill tumor cells, as well as higher production of interferon-γ and tumor necrosis factor-α, compared with the no-HDP-treated CIK cells. The HDP-treated CIK cells also found a lower apoptosis level in vitro. Moreover, HDP combined with CIK cells had a stronger inhibitory effect on tumor growth in the mouse model compared with the CIK or HDP treatment alone. In conclusion, the results indicated that HDP enhanced the antitumor activity of CIK cells and could be used for cancer immunotherapy combined with CIK cell therapy.

Characterization of a polysaccharide HP-02 from Honeysuckle flowers and its immunoregulatory and anti-Aeromonas hydrophila effects in Cyprinus carpio L.

Aquaculture systems are known to be major reservoirs of Aeromonas hydrophila. The use of Chinese medicinal polysaccharides has become a successful strategy to prevent bacterial diseases in aquaculture. A water-soluble polysaccharide, HP-02, was purified from honeysuckle flowers, and the present study was aimed to examine its immunomodulatory and anti-A. hydrophila effects in Cyprinus carpio L. The results showed that the molecular weight of HP-02 was estimated to be 38 kDa. Monosaccharide composition was determined to be arabinose, rhamnose, mannose, glucose, and galactose in a molar ratio of 2.5: 1.8: 3.6: 3.7: 1.9. HP-02 not only distinctly improved the proliferation and phagocytosis of head kidney cells, but also exerted significant immunoregulation activity by increasing the secretion of the pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and IL-12 and the anti-inflammatory cytokines IL-10 and TGF-ß at the protein level in head kidney cells and serum. Moreover, during pathogen infection in vivo, HP-02 significantly reduced the expression of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines. These results indicated that HP-02 had immunomodulatory effects on common carp both in vitro and in vivo, and HP-02 can be applied as a common carp feed supplement to enhance fish immunity and disease resistance against A. hydrophila.

Signaling pathways associated with macrophage-activating polysaccharides purified from fermented barley.

Barley is commonly used in many food and health products. We have previously demonstrated the macrophage-stimulating properties of polysaccharides derived from fermented barley. In this study, three polysaccharide fractions (BF-I-III) were purified from fermented barley and their monosaccharide composition was analyzed. Their immune-stimulatory activities and intracellular signaling pathways were also studied in RAW264.7 cells. Among the three fractions, BF-I exhibited enhanced macrophage activation properties, such as inducing the production of IL-6, IL-12, and TNF-α. However, BF-II and BF-III showed moderate effects on RAW 264.7 cells. BF-I treatment led to the phosphorylation of MAPKs, NF-κB, and c-Jun (major component of AP-1 transcription factor) and induced the nuclear translocation of p65 in RAW264.7 cells. In addition, experiments with neutralizing antibodies showed that Dectin-1, toll-like receptor (TLR) 4, scavenge receptor (SR), and CD14 were mainly involved in the stimulation of nitric oxide (NO) production by BF-I which was suppressed by the inhibition of JNK phosphorylation. These findings suggest that BF-I, isolated from fermented barley, has an immune potentiation activity on macrophages, where it activates the JNK signaling pathway via several macrophage receptors including dectin-1, TLR4, SR, and CD14.

Immunological modulation effects of an acid Epimedium polysaccharide on immune response in chickens.

The purpose of the present study is to investigate the immunological activities of EPS-1 in the non-specific immune response and specific immune response of chickens. In vitro, the results showed that EPS-1 could increase the proliferation and cytokine secretion (IL-2, IL-4, IFN-γ and TNF-α) of spleen lymphocytes, expression of key surface molecules (MHC II, CD11c, CD40 and CD86) and cytokine secretion (TNF-α and IL-10) of matured chBM-DCs, phagocytic rate of matured chBM-DCs, and enhance the maturation and stimulating capacity of chBM-DCs. In vivo, EPS-1 could also prompt the HI antibody titer, boost the peripheral lymphocyte proliferation, enhance the release of cytokine products in blood (IFN-γ, IL-4 and IL-2) and duodenum (IL-17 and sIgA) of chickens. These results indicated that EPS-1 may have the potential as a powerful immune adjuvant in the treatment of chicken diseases.

Discrimination of Structural and Immunological Features of Polysaccharides from Persimmon Leaves at Different Maturity Stages.

In this study, we investigated changes in the structural and immunological features of polysaccharides (S1-PLE0, S2-PLE0, and S3-PLE0) extracted from persimmon leaves at three different growth stages. Physicochemical analyses revealed that their chemical compositions, molecular weight distributions, and linkage types differed. High-performance size-exclusion chromatograms showed that the molecular weights of the polysaccharides increased during successive growth stages. In addition, seasonal variation of persimmon leaves affected the sugar compositions and glycosidic linkages in the polysaccharides. S2-PLE0 was composed of comparatively more galactose, arabinose, rhamnose, xylose, and galacturonic acid, showing the presence of ß-glucopyranoside linkages. Significant differences also occurred in their immunostimulatory effects on RAW264.7 macrophages, with respect to which their activities could be ordered as S2-PLE0 > S3-PLE0 > S1-PLE0. Evidently, S2-PLE0 showed the greatest immunostimulatory activity by enhancing the phagocytic capacity and promoting nitric oxide (NO) and cytokines secretion through the upregulation of their gene expression in macrophages. These results suggest that differences in the structural features of polysaccharides according to the different maturity of persimmon leaves might impact their immunostimulatory properties. The results also provide a basis for optimizing persimmon leaf cultivation strategies for food and medical uses of the polysaccharides.

Molecular properties and immunomodulatory activities of a water-soluble heteropolysaccharide isolated from Plantago asiatica L. leaves.

This study aims at investigating physical-chemical properties of a water-soluble heteropolysaccharide from Plnatago asiatica L. leaves, and its immunomodulatory effects on macrophages RAW264.7 cells. Hot water-extracted crude polysaccharide from the plant leaves (PLLCP) was fractionated into four fractions by DEAE Sepharose Fast Flow eluted with 0.1-0.5 M NaCl solutions. The most abundant fraction (0.3 M NaCl elution), designated PLLP-2, was identified as a heteropolysaccharide with an average molecular weight (Mw) of 3.54 × 104 and composed mainly of Gal (34.4%), GalA (36.5%), Ara (10.1%) and Rha (8.4%). PLLP-2 was an acidic polysaccharide exhibiting inflaky curly aggregation with smooth surface. PLLCP and its main subfraction PLLP-2 displayed immunomodulatory activities by stimulating the production of pro-inflammatory cytokines, including TNF-α and IL-1ß in macrophage RAW264.7 cells. These results indicate that the main polysaccharide fraction purified from P. asiatica L. leaves is probably pectin, and have potential immunomodulatory function.

Structure Dependent-Immunomodulation by Sugar Beet Arabinans via a SYK Tyrosine Kinase-Dependent Signaling Pathway.

There is much interest in the immunomodulatory properties of dietary fibers but their activity may be influenced by contamination with microbial-associated molecular patterns (MAMPs) such as lipopolysaccharide (LPS) and lipoteichoic acids, which are difficult to remove completely from biological samples. Bone marrow-derived dendritic cells (BMDCs) from TLR2x4 double-KO mice were shown to be a reliable approach to analyse the immunomodulatory properties of a diverse range of dietary fibers, by avoiding immune cell activation due to contaminating MAMPs. Several of the 44 tested dietary fiber preparations induced cytokine responses in BMDCs from TLR2x4 double-KO mice. The particulate fractions of linear arabinan (LA) and branched arabinan (BA) from sugar beet pectin were shown to be strongly immune stimulatory with LA being more immune stimulatory than BA. Enzymatic debranching of BA increased its immune stimulatory activity, possibly due to increased particle formation by the alignment of debranched linear arabinan. Mechanistic studies showed that the immunostimulatory activity of LA and BA was independent of the Dectin-1 recognition but Syk kinase-dependent.

Polysaccharides as vaccine adjuvants.

Adjuvant is a substance added to vaccine to improve the immunogenicity of antigens, and it can induce stronger immune responses and reduce the dosage and production cost of vaccine in populations responding poorly to vaccination. Adjuvants in development or in use mainly include aluminum salts, oil emulsions, saponins, immune-stimulating complexes, liposomes, microparticles, nonionic block copolymers, polysaccharides, cytokines and bacterial derivatives. Polysaccharide adjuvants have attracted much attention in the preparation of nano vaccines and nano drugs because natural polysaccharides have the characteristics of intrinsic immunomodulating, biocompatibility, biodegradability, low toxicity and safety. Moreover, it has been proved that a variety of natural polysaccharides possess better immune promoting effects, and they can enhance the effects of humoral, cellular and mucosal immunities. In the present study, we systematically reviewed the recent studies on polysaccharides with vaccine adjuvant activities, including chitosan-based nanoparticles (NPs), glucan, mannose, inulin polysaccharide and Chinese medicinal herb polysaccharide. The application and future perspectives of polysaccharides as adjuvants were also discussed. These findings lay a foundation for the further development of polysaccharide adjuvants. Collectively, more and more polysaccharide adjuvants will be developed and widely used in clinical practice with more in-depth investigations of polysaccharide adjuvants.