Dendritic cells restrict the transformation of Histoplasma capsulatum conidia into yeasts.

Infections due to Histoplasma capsulatum occur as a result of the inhalation of airborne microconidia of the mold into the alveoli of the lungs. In this study we quantified the transformation over time of conidia into yeast-like cells within macrophages (MΦ) and dendritic cells (DC). Conidia from strain G217B which had been surface labeled with carboxy-fluorescein succinimidyl ester (CFSE), or conidia from strain G217B that expresses green fluorescent protein (GFP) only in the yeast phase, were used to infect MΦ and DC. At various time points, numbers of intracellular conidia or yeasts were quantified via phase-contrast and fluorescent microscopy. Transformation of conidia from non-GFP-expressing G217B also was quantified by their incorporation of ³H-leucine. In both human and murine MΦ, numerous yeast-like cells appeared by day 3 post-infection. The time course of conidia transformation into yeasts in culture medium was the same as in MΦ. However, transformation of conidia to yeasts was significantly restricted in human DC and murine lung DC. In DC, significant numbers of yeasts did not appear until 5 days post-infection. Further, MΦ monolayers were destroyed by day 6-7 post-infection, whereas DC monolayers remained intact throughout the study period. These data suggest that in vivo, conidia may transform into yeast-like cells efficiently whether or not they are phagocytosed by MΦ, but not when ingested by DC.