1. Cell wall N-glycan of Candida albicans ameliorates early hyper- and late hypo-immunoreactivity in sepsis.
- Author
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Kawakita M, Oyama T, Shirai I, Tanaka S, Akaki K, Abe S, Asahi T, Cui G, Itoh F, Sasaki M, Shibata N, Ikuta K, Hatakeyama T, and Takahara K
- Subjects
- Animals, Candida albicans metabolism, Candidiasis metabolism, Candidiasis microbiology, Cell Wall metabolism, Cells, Cultured, Cytokines metabolism, Dendritic Cells immunology, Dendritic Cells metabolism, Disease Models, Animal, Host-Pathogen Interactions, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-10 immunology, Interleukin-10 metabolism, Interleukin-1beta immunology, Interleukin-1beta metabolism, Lectins, C-Type genetics, Lectins, C-Type metabolism, Macrophages immunology, Macrophages metabolism, Membrane Glycoproteins metabolism, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Polysaccharides metabolism, Sepsis metabolism, Sepsis microbiology, T-Lymphocytes immunology, T-Lymphocytes metabolism, Time Factors, Tumor Necrosis Factor-alpha immunology, Tumor Necrosis Factor-alpha metabolism, Mice, Candida albicans immunology, Candidiasis immunology, Cell Wall immunology, Cytokines immunology, Membrane Glycoproteins immunology, Polysaccharides immunology, Sepsis immunology
- Abstract
Severe infection often causes a septic cytokine storm followed by immune exhaustion/paralysis. Not surprisingly, many pathogens are equipped with various anti-inflammatory mechanisms. Such mechanisms might be leveraged clinically to control septic cytokine storms. Here we show that N-glycan from pathogenic C. albicans ameliorates mouse sepsis through immunosuppressive cytokine IL-10. In a sepsis model using lipopolysaccharide (LPS), injection of the N-glycan upregulated serum IL-10, and suppressed pro-inflammatory IL-1β, TNF-α and IFN-γ. The N-glycan also improved the survival of mice challenged by LPS. Analyses of structurally defined N-glycans from several yeast strains revealed that the mannose core is key to the upregulation of IL-10. Knocking out the C-type lectin Dectin-2 abrogated the N-glycan-mediated IL-10 augmentation. Furthermore, C. albicans N-glycan ameliorated immune exhaustion/immune paralysis after acute inflammation. Our results suggest a strategy where the immunosuppressive mechanism of one pathogen can be applied to attenuate a severe inflammation/cytokine storm caused by another pathogen.
- Published
- 2021
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