Importance of Candida Antigenic Factors: Structure-Driven Immunomodulation Properties of Synthetically Prepared Mannooligosaccharides in RAW264.7 Macrophages

Abstract

The incidence and prevalence of serious fungal infections is rising, especially in immunosuppressed individuals. Moreover, co-administration of antibiotics and immunosuppressants has driven the emergence of new multidrug-resistant pathogens. The significant increase of multidrug-resistant pathogens, together with their ability to form biofilms, is associated with morbidity and mortality. Research on novel synthetically prepared immunomodulators as potential antifungal immunotherapeutics is of serious interest. Our study demonstrated the immunobiological activity of synthetically prepared biotinylated mannooligosaccharides mimicking Candida antigenic factors using RAW264.7 macrophages. Macrophage exposure to the set of eight structurally different mannooligosaccharides induced a release of Th1, Th2, Th17, and Treg cytokine signature patterns. The observed immune responses were tightly associated with structure, dose, exposure time, and selected signature cytokines. The viability/cytotoxicity of the mannooligosaccharide formulas was assessed based on cell proliferation. The structure-based immunomodulatory activity of the formulas was evaluated with respect to the length, branching and conformation of the various formulas. Glycoconjugate formulas with terminal β-mannosyl-units tended to be more potent in terms of Candida relevant cytokines IL-12 p70, IL-17, GM-CSF, IL-6, and TNFα induction and cell proliferation, and this tendency was associated with structural differences between the studied glycoconjugate formulas. The eight tested mannooligosaccharide conjugates can be considered potential in vitro immunomodulative agents suitable for in vitro Candida diagnostics or prospectively for subcellular anti-Candida vaccine design.

Immunomodulatory activity of mannosylglycerate and two unnatural mannosyl‐oligosaccharides obtained from microbial fermentation on RAW264.7 macrophages

“…By contrast, 500-1000 μg ml −1 M3-β-1,4 significantly inhibited the proliferation of macrophages (Figure 2a). In a previous study, Paulovicová demonstrated that treatment with synthetically prepared biotinylated mannooligosaccharides containing β-1,2-linked mannosyl units terminus could significantly increase the proliferation of RAW264.7, consistent with the findings of the present study (Paulovicova et al, 2019). Therefore, 125 and 250 μg ml −1 of MG, 1000 and 2000 μg ml −1 of M2-β-1,2, 250 and 500 μg ml −1 of M3-β-1,2, 250 and 500 μg ml −1 of M3-β-1,4 were selected for the following assays.…”

Unique Cell Surface Mannan of Yeast Pathogen Candida auris with Selective Binding to IgG

“…Mannoproteins are adhesins (mannans with lectin-like properties , ) and promote Candida binding to endothelial and epithelial cells. − Different Candida species have different glycan structures − Fungal mannan antigenemia is also regarded as a diagnostic indicator of invasive Candida infections. , At present, we know little about the cell wall, the mannoproteins, mannans, and the glycome of C. auris .…”

Conjugation of Hemoglobin and Mannan Markedly Improves the Immunogenicity of Domain III of the Zika Virus E Protein: Structural and Immunological Study

“…Hb and mannan both functioned as the adjuvants. As an oxygen carrier, Hb was a potential immunomodulatory protein without a significant adverse immune effect, which could regulate inflammation, cytokine secretion, and activation of macrophage in the plasma. , Mannan was a ligand of TLR-4 or TLR-2 and could be recognized via mannose receptor, dectin-2, and DC-SIGN, which induce Th1-type and Th2-type immune response. − Hb and mannan could play the immunomodulatory activities in a synergistic manner. Consistently, physical administration of HM with EDIII was demonstrated to increase the immunogenicity of EDIII in the present study.…”