Hormones and the resistance of women to paracoccidioidomycosis

Abstract

Paracoccidioidomycosis, one of the most important endemic and systemic mycoses in Latin America, presents several clinical pictures. Epidemiological studies indicate a striking rarity of disease (but not infection) in females, but only during the reproductive years. This suggested a hormonal interaction between female hormones and the etiologic dimorphic fungus Paracoccidioides brasiliensis. Many fungi have been shown to use hormonal (pheromonal) fungal molecules for intercellular communication, and there are increasing numbers of examples of interactions between mammalian hormones and fungi, including the specific binding of mammalian hormones by fungal proteins, and suggestions of mammalian hormonal modulation of fungal behavior. This suggests an evolutionary conservation of hormonal receptor systems. We recount studies showing the specific hormonal binding of mammalian estrogen to proteins in P. brasiliensis and an action of estrogen to specifically block the transition from the saprophytic form to the invasive form of the fungus in vitro. This block has been demonstrated to occur in vivo in animal studies. These unique observations are consistent with an estrogen-fungus receptor-mediated effect on pathogenesis. The fungal genes responsive to estrogen action are under study.

Fig. 1.

Stages in the conidium-to-yeast transition in the lungs of mice (stained with Gomori methenamine silver). (A) Conidia. An inoculum was obtained from the mycelial phase, as seen in bronchoalveolar lavage fluid 1 h postchallenge. Magnification, ×40. (B) Intermediate cells noted to be developing in males at 48 h postchallenge. Magnification, ×100. (C). Yeast cells seen in males at 48 to 96 h postchallenge. Magnification, ×100. Note that the diameters of yeast cells are twice those of intermediate cells, and note the reproduction by (multiple) budding in yeasts in the right half of the figure. (Courtesy of Beatriz Aristizabal, reproduced with permission.)

Fig. 2.

Histological observation of the lungs of mice 2 weeks after intranasal infection with P. brasiliensis conidia. A granulomatous reaction in a male mouse and a lack of inflammatory reaction in a female mouse are contrasted. (hematoxylin and eosin staining; magnifications are shown). (Courtesy of Beatriz Aristizabal, reproduced with permission.)