An iC3b Receptor on Candida albicans: Structure, Function, and Correlates for Pathogenicity

Abstract

Heretofore, the existence of membrane receptors for biologically active fragments of mammalian complement proteins has been confined to mammalian cells, where these receptors serve to protect the host by triggering multiple aspects of the phagocytic response to microbial invasion. In this study, we show that surface receptors for the C3 fragment iC3b are present on the yeast Candida albicans, where they promote the pathogenicity of this organism by inhibiting phagocytosis. These receptors share homology with the alpha-chain, but not with the beta-chain, of neutrophil receptors for iC3b, as determined by the binding of monoclonal antibodies, and are induced by mycelial transformation of the yeast and by high concentrations of glucose. Blockade of these receptors by monoclonal antibodies significantly augments phagocytosis for those strains studied. By binding iC3b noncovalently, these receptors impair phagocytic uptake of C. albicans by human polymorphonuclear leukocytes.

Molecular mimicry in Candida albicans. Role of an integrin analogue in adhesion of the yeast to human endothelium.

“…We have recently described a surface protein on yeastphase C. albicans that shares antigenic and structural homology with the a-subunit of the leukocyte adhesion glycoprotein CD1 lb/CD 18, also known as Mol, Mac-l, the iC3b receptor, or complement receptor type 3 (CR3); CD1 lb/CD 18 is found on mammalian neutrophils, monocytes, and macrophages (18)(19)(20)(21). MAbs that recognize the a subunit of CD1 lb/CD 18 bind specifically to yeast-or hyphal-phase C. albicans, while isotype controls do not (18)(19)22).…”

“…MAbs that recognize the a subunit of CD1 lb/CD 18 bind specifically to yeast-or hyphal-phase C. albicans, while isotype controls do not (18)(19)22). Increases in ambient temperature to 37°C result in increased expression of CDl lb/ CD1 8 in the neutrophil and of its analogue in C. albicans (18,(23)(24) do not bind specifically to C. albicans, as assessed by flow cytometry or fluorescent microscopy (18,19,22). After a 30-min incubation on ice with murine MAb, yeasts were centrifuged and washed three times with PBS/0.02% azide.…”

Murine candidiasis: Sex differences in the severity of tissue lesions are not associated with levels of serum C3 and C5

“…No other instances of sex-determined differences in concentrations of serum C3 have yet been reported. As there are no known differences in the structure or function of C3 derived from male and female animals, it seems quite improbable that there would be any significant difference between the sexes either in the activation and/or utlization of C3 by sub-lethal challenge with C. albicans or in the binding of C3 fragments by the C3 receptor on the yeast itself (21). Therefore, two firm conclusions can be drawn from the data.…”

Society for Pediatric Research Presidential Address 1994: Yeast as Metaphor

“…~r o w t h of yeast cells in medium containing 220 mM D-glucose, growth in the presence of M hydrocortisone, or growth at 37°C-all increase expression of the integrin analog in C. albicans by as much as 2-to 6-fold (4,5). These conditions suggest not only possible clinical correlates but potential regulators of integrin gene expression as well.…”