Beta-mannosyl linkages negatively regulate anaphylaxis and vasculitis in mice, induced by CAWS, fungal PAMPS composed of mannoprotein-beta-glucan complex secreted by Candida albicans

Abstract

Candida albicans water soluble fraction (CAWS) is a water-soluble extracellular mannoprotein-beta-glucan complex obtained from the culture supernatant of Candida albicans, which grows in a chemically defined medium. CAWS induced toxic reactions, such as acute anaphylactoid reaction, by intravenous administration and coronary arteritis by intraperitoneal administration. To clarify the structure responsible for these toxic reactions, C. albicans was cultured in pH- and temperature-controlled conditions and prepared with CAWS with or without the beta-1,2-linked mannosyl segment (BM). The structure of CAWS was assessed by immunochemical and spectroscopic methodologies, and we found that CAWS prepared under the natural culture conditions contained only small amounts of BM and CAWS prepared at neutral conditions at 27 degrees C contained a significantly higher percentage of BM. Both the acute lethal toxicity and coronary arteritis induction was significantly more severe in the absence of BM. Activation of a complement pathway, the lectin pathway, by CAWS was significantly stronger in the absence of BM. These facts strongly suggest that BM linkages in CAWS negatively modulate acute and chronic toxicity of CAWS, and may be strongly related to the lectin pathway of the complement activation.