Differential humoral response against alpha- and beta-linked mannose residues associated with tissue invasion by Candida albicans

Abstract

Candida albicans mannan is the major cell wall antigen that elicits antibodies considered to be of little diagnostic value. It comprises epitopes corresponding to sequences of ␣-and ␤-1,2-linked mannose residues. Both types of oligomannosidic epitopes may also be present on the glycosidic portions of other C. albicans molecules, i.e., mannoproteins (MP) (either structural or enzymatic) and glycolipids. The human humoral responses against ␤-1,2-and ␣-linked oligomannosides were investigated by C. albicans Western blotting by considering the elective distribution of ␤-1,2-oligomannosidic epitopes over a 14-to 18-kDa phospholipomannan (PLM) and the presence of ␣-mannosidic epitopes over heavily glycosylated MP. Western blotting of 51 control sera confirmed the presence of antibodies against C. albicans as a commensal member of the indigenous microflora; an immunoglobulin G (IgG) reactivity linked to enzyme-linked immunosorbent assay mannan signals was found for both PLM (␤-1,2-Man residues) and MP (␣-Man residues). Despite strong reactivities against mannan and MP, IgG from 21 hospitalized patients with mycological evidence of deep-tissue invasion by C. albicans very significantly failed to react or reacted only faintly with PLM. This downregulation of anti-␤-1,2-oligomannosidic epitopes, associated with tissue invasion by C. albicans, was confirmed in 3 of 4 AIDS patients with extended oroesophageal candidosis. The application of a dissociation procedure proved that the absence of PLM reactivity was not due to the presence of immune complexes. These data provide the first evidence for a qualitative modification of the human antimannan antibody response associated with the C. albicans commensal-pathogenic transition.

Nature ofCandida albicans-derived carbohydrate antigen recognized by a monoclonal antibody in patient sera and distribution overCandidaspecies

“…Similarly, the synthesis of anti‐α and anti‐β oligomannoside antibodies has been shown to be differently regulated in patients colonized and infected by C . albicans [23]. Together, these data emphasize the importance of a comprehensive approach involving structure/immunoreactivity of C .…”

Dissection of the anti-Candida albicans mannan immune response using synthetic oligomannosides reveals unique properties of β-1,2 mannotriose protective epitopes

“…Its structure has been well established by an impressive series of structural and serological studies from Suzuki's group 26 , 27 . These authors established that C. albicans mannan is similar to the mannan of the closely related species S. cerevisiae , extensively studied as a model of glycosylation, with a comb-shaped structure composed of α-1,2, α-1,3, and α-1,6 mannose residues, but that C. albicans , C. tropicalis and C. glabrata , now reported as responsible for 90% of human Candida infections 28 , also have the ability to synthesize β1,2 mannose 4 , 21 , 29 , 30 .…”

Candida albicansandSaccharomyces cerevisiaeinduce interleukin-8 production from intestinal epithelial-like Caco-2 cells in the presence of butyric acid

“…Candida albicans is known to produce phospholipomannan, mannoprotein, proteinases, and high‐affinity iron permease, all of which are considered virulent factors [32–34]. In addition, C. albicans has been shown to form germ tubes in response to environmental factors, such as temperature, pH, hemin, or some serum components [35–37].…”