Abstract
Candidiasis is common in diabetic patients. Complement evasion is facilitated by binding complement factor H (FH). Since the expression of high-affinity glucose transporter 1 (Hgt1), a FH-binding molecule, is glucose-dependent, we aimed to study its relevance to the pathogenesis of Candida albicans. Euglycemic and diabetic mice were intravenously challenged with either Candida albicans lacking Hgt1 (hgt1-/-) or its parental strain (SN152). Survival and clinical status were monitored over 14 days. In vitro, Candida albicans strains were grown at different glucose concentrations, opsonized with human serum, and checked for C3b/iC3b and FH deposition. Phagocytosis was studied by fluorescein isothiocyanate-labeled opsonized yeast cells incubated with granulocytes. The murine model demonstrated a significantly higher virulence of SN152 in diabetic mice and an overall increased lethality of mice challenged with hgt1-/-. In vitro lower phagocytosis and C3b/iC3b deposition and higher FH deposition were demonstrated for SN152 incubated at higher glucose concentrations, while there was no difference on hgt1-/- at physiological glucose concentrations. Despite C3b/iC3b and FH deposition being glucose-dependent, this effect has a minor influence on phagocytosis. The absence of Hgt1 is diminishing this dependency on complement deposition, but it cannot be attributed to being beneficial in a murine model.
Highlights
The complement system plays a central role in innate immunity, bridging the innate and the adaptive immune defense [1]
Absence of high-affinity glucose transporter 1 (Hgt1) or C3 Increases the Virulence of Candida albicans in a Murine Model of Systemic Candidiasis
We here analyzed the relevance of the complement system, as an essential part of the innate immunity, and glucose on the pathogenesis of Candida albicans
Summary
The complement system plays a central role in innate immunity, bridging the innate and the adaptive immune defense [1] This complex system consists of over 40 proteins, soluble plasma factors, cell-associated regulator molecules, and receptors [2]. After an appropriate surface-bound or soluble pattern recognition receptor gets in contact with either pathogen-associated molecular patterns or foreign cellular structures such as cell debris or non-self-tissue, the activation starts within seconds. This activation can take place by three pathways, the classical (CP), the lectin (LP), and the alternative pathway (AP). The nonenzymatically sequentially activated C7, C8, and C9 adhere to C5b6 to form this complex, which can either exist in soluble form or produce a lytic pore as a membrane–attack complex (MAC) [1]
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