Morphological transition of Paracoccidioides brasiliensis conidia to yeast cells: in vivo inhibition in females

Abstract

Clinical paracoccidioidomycosis is 13 times more common in men than in women. Estrogen inhibits the transition of mycelia or conidia (the saprophytic form of Paracoccidioides brasiliensis) to yeasts (the parasitic form) in vitro. Here, we show that, in male mice that were infected intranasally (mimicking natural infection) the transition of conidia in bronchoalveolar lavage fluids to intermediate forms and yeasts occurred over 24 to 96 h; CFU and yeasts (shown by histopathology) increased subsequently. In females, transition did not occur and infection cleared. These events in vivo are consistent with epidemiological and in vitro observations, suggesting that female hormones block transition and are responsible for resistance.

FIG. 1

Appearance of P. brasiliensis cells at 1, 24, 48, 72, and 96 h, in the BAL fluids of mice infected intranasally with C. Data are pooled results from two experiments (n = 6, except for females at 96 h, n = 5) and show total fungal cells (A) and percentages of total cells as C (B), INT (C), and Y (D). C. I., confidence interval; SD, standard deviation.

FIG. 2

Stages in the C-to-Y transition in lungs of mice. (A) Inoculum of C obtained from M phase in BAL fluid 1 h postchallenge, stained with GMS. Magnification, ×40. (B) INT cells developing in males 48 h postchallenge, stained with GMS. Magnification, ×100. (C) Y cells in males 48 to 96 h postchallenge, stained with GMS. Magnification, ×100. Note that the diameter of Y (cells in the plane of focus) is twice that of cells in panel B, and note the reproduction by budding in Y.

FIG. 2

Stages in the C-to-Y transition in lungs of mice. (A) Inoculum of C obtained from M phase in BAL fluid 1 h postchallenge, stained with GMS. Magnification, ×40. (B) INT cells developing in males 48 h postchallenge, stained with GMS. Magnification, ×100. (C) Y cells in males 48 to 96 h postchallenge, stained with GMS. Magnification, ×100. Note that the diameter of Y (cells in the plane of focus) is twice that of cells in panel B, and note the reproduction by budding in Y.

FIG. 3

Histological observation of the lungs of mice 2 to 6 weeks after intranasal infection with P. brasiliensis C. (A) Chronic granulomatous reaction in a male mouse (hematoxylin and eosin stain; magnification, ×40). (B) Lung section with no inflammatory reaction in a female mouse (hematoxylin and eosin stain; magnification, ×40).