ALTERED EXPRESSION OF SURFACE PROTEIN WI-1 IN GENETICALLY RELATED STRAINS OF BLASTOMYCES-DERMATITIDIS THAT DIFFER IN VIRULENCE REGULATES RECOGNITION OF YEASTS BY HUMAN MACROPHAGES

The molecular basis for pathogenicity and virulence of the dimorphic f ungus Blastomyces dermatitidis remains unknown. WI-1 is a major cell w all protein of B. dermatitidis yeasts and is a recognition target of b oth humoral and cell-mediated immunity. As an initial study to determi ne if WI-1 might be linked to virulence of B. dermatitidis, we quantif ied WI-1 expression on three genetically related strains that differ i n their virulence for mice: wild-type virulent ATCC strain 26199, muta nt ATCC strain 60915 (which is 10,000-fold reduced in virulence), and mutant ATCC strain 60916 (which is avirulent). Two principal alteratio ns in WI-1 expression were observed in the mutants. First, the mutants express more WI-1 on their surface, as quantified by flow cytometry w ith monoclonal antibody to WI-1 and by radioimmunoassay, but the WI-1 on their cell wall is less extractable than that on the wild-type stra in. Second, the mutants shed less WI-1 during culture and demonstrate impaired professing of shed WI-1. Surface alterations in WI-1 were acc ompanied by significant differences in the binding of the virulent and mutant strains to human monocyte-derived macrophages. Attachment of y easts to macrophages paralleled and was proportional to the expression of WI-1. Compared with wild-type yeasts, both mutants bound to macrop hages more rapidly and in two- to threefold-greater magnitude. Further more, about 75% of yeast binding to macrophages was inhibited by a Fab anti-WI-1 monoclonal antibody. These results suggest that altered WI- 1 expression on attenuated and avirulent mutant B. dermatitidis yeasts greatly facilitates macrophage recognition and binding of yeasts and, in turn, may contribute to more rapid ingestion and killing in the ho st.