Evidence that mannans of Candida albicans are responsible for adherence of yeast forms to spleen and lymph node tissue

Abstract

We have described a unique binding system between Candida albicans yeast-form cells and the marginal zone of mouse spleen (16). The chemical nature of the fungal adhesin(s) involved in this binding phenomenon was examined. A fraction obtained by 2-mercaptoethanol extraction (2-ME extract) of fungal cells caused a dose-response inhibition of yeast cell adherence to splenic marginal zone sites and also to subcapsular and medullary sinuses of mouse popliteal lymph nodes. Latex beads coated with the 2-ME extract showed a pattern of spleen and lymph node tissue binding identical to that observed with yeast cells. The extracted adhesins retained their binding activity in vivo. When 0.5 mg of the 2-ME extract was given intravenously to mice, spleen tissue removed up to 3 h later showed over 80% inhibition of yeast cell binding to the spleen marginal zone, and over 50% inhibition was retained for at least 24 h. The adhesins bound to a concanavalin A affinity column and were eluted by 0.5 M alpha-methyl-D-mannopyranoside, and the eluted adhesins were designated Fr.II. Fr.II was further fractioned by DEAE-Sephacel ion-exchange column chromatography, and one especially active and abundant fraction was designated Fr.IIa. The adhesin moiety appeared to be carbohydrate, because the activity of Fr.IIa was destroyed by 20 mM sodium periodate or by 5 U of alpha-mannosidase, but boiling (30 min) or proteinase K (100 micrograms/ml) treatments had no effect. Chemically, whereas the 2-ME extract contained significant amounts of protein and mannose, Fr.IIa consisted of over 98% mannose and less than 0.5% protein. These data strongly suggest that the mannan portion within a mannoprotein is responsible for the binding of yeast cells to splenic marginal zone and to subcapsular and medullary sinuses of mouse lymph node tissue.