A potential histoplasmosis pathogenesis mechanism mediated by a lectin of Histoplasma capsulatum with affinity to β-galactose, favoring intravascular hemagglutination.

Ascomycetes belonging to the Histoplasma capsulatum species complex can cause severe manifestations in patients with disseminated histoplasmosis. Based on data from hemagglutination assays and histopathological findings related to H. capsulatum, we investigated their potential role in the disseminated intravascular hemagglutination events. Human erythrocyte hemagglutination was produced with H. capsulatum yeasts of 10 isolates/strains, belonging to different phylogenetic species and lineages. Hemagglutination assays were inhibited by pre-incubating their yeasts with β-galactose, ratifying previously published data for a unique H. capsulatum clinical strain. This lectin was partially purified through affinity chromatography using erythrocyte stroma, and its hemagglutinating activity was confirmed. Results underlined the consistent involvement of a β-galactose-binding lectin of H. capsulatum yeasts in hemagglutination assays by using genetically distinct H. capsulatum species, which support its conserved origin. Serendipitous findings in histopathological sections of human and bat tissues supported that H. capsulatum yeasts adhered to erythrocytes, consistent with intravascular hemagglutination. Hence, in hosts with disseminated histoplasmosis and sepsis, we hypothesized that this H. capsulatum lectin may favor an intravascular hemagglutination, which could occur concomitantly with a procoagulant state, aggravating hypoxia and leading to disseminated intravascular coagulation, a lethal complication.