SUMMARYFemale albino rats were used for the sequential histopathological study of experimental paracoccidioidomycosis. The animals were inoculated intraperitoneally with a strain of Paracoccidioides brasiliensis in the yeast-like phase, and sacrificed at given intervals from 1 to 168 days after inoculation; each animal received an inoculum of 4 x 10^ cells in 0.8 ml of saline. The control group received saline containing scrapings of the culture medium.Tissue from the inoculation site was examined. The cellular population, the extracellular matrix, and the presence and characteristics of fungi were analysed in the inflammatory granulomatous process by light microscopy.The results allowed to separate the kinetic of the inflammatory response into three stages: 1) neutrophilic or macrophagic-neutrophilic; 2) pre-granulomatous; 3) granulomatous.Synthesis of the extracellular matrix began with the depositing of fibrin-like material, and increased gradually with deposits of collagen, proteoglycans, and glycoproteins. Parasites were present in all of the examined periods.Recurrences of the disease were clearly shown through the concurrence of recently-formed granulomas with older granulomas, implying that this type of granulomatous process does not eliminate the disease, nor is it able to limit fungal dissemination over a prolonged period of time.
The histological and ultrastructural aspects of chronic granulomas from rats infected intraperitoneally with Paracoccidioides brasiliensis are described with special emphasis on the composition of the extracellular matrix. The granulomas were structurally arranged in two zones, one central containing fungi, and the other peripheral. The extracellular matrix was composed of collagen types I and III, proteoglycans, glycoprotein, and an undefined amorphous substance. The main cellular population was represented by macrophages, epithelioid cells, and giant cells in the central zone, and fibroblasts in the peripheral zone. The fibrotic process was a critical event in this stage of the infection, and showed a centrifugal direction. This might be provoked by direct stimulus from the fungi or by macrophage-fibroblastic interaction.
The development of intraperitoneal paracoccidioidomycosis was studied in groups of female and male rats: a) Under normal conditions (intacts), b) After castration and c) After castration but submitted to a treatment with, respectively, testosterone and estradiol. The criterion of susceptibility to infection was based on: 1) Spontaneous mortality of the animals and 2) Number of metastatic pulmonary lesions. The results showed that: the unique deaths and the more severe pulmonary lesions were found among the intact females, representing the animals most susceptible to the infection in these experiments; the intact females showed more numerous lesions than the castrated; the intact males had less lesions than the castrated, and than those castrated which were treated with estradiol.
Congenitally athymic nude mice (nu/nu) and their phenotypically normal littermates (nu/+) were intraperitoneally infected with yeast cells of a strain of Paracoccidioides brasiliensis. The nude mice developed a severe and generalized infection with an intense parasitism of several organs, accompanied by a low-grade of tissue reaction. The lesions were characterized by abundant yeast-like cells of the fungus, and in some animals, numerous hyphal forms could be well visualized. In control animals, infection was moderate, almost exclusively restricted to the area of inoculation, and the lesions presented few parasites surrounded by an inflammatory response. Filamentous forms of the fungus were never encountered in these animals.
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