Murine model of paracoccidioidomycosis. Production of fatal acute pulmonary or chronic pulmonary and disseminated disease: immunological and pathological observations.

A model of fatal acute pulmonary or chronic pulmonary and disseminated paracoccidioidomycosis was developed by intranasal challenge of young (3-4-week-old) mice with high doses (2.5-10 X 10(7) units) or low doses (0.1-1 X 10(7)) of yeast-phase Paracoccidioides brasiliensis. Fatal acute paracoccidioidomycosis was dose dependent; 10, 5, and 2.5 X 10(7) viable units of P. brasiliensis produced 100%, 66%, and 17% mortality, respectively, within 11 days. The pathologic picture was that of consolidation with a neutrophil infiltrate. Infection of adult (7-8-week-old) mice with even 10 X 10(7) units did not produce acute fatal paracoccidioidomycosis. The model of fatal acute paracoccidioidomycosis lends itself well to studies of therapeutic intervention. Increasing degrees of chronic pulmonary-disseminated paracoccidioidomycosis were produced by pulmonary infection of young mice with 0.1-1 X 10(7) viable units of P. brasiliensis. Although mice in all groups appeared healthy, pathology in lungs, liver, and spleen was evident at 7 and 10 weeks postinfection. Histopathologic observation revealed acinonodular granulomatous inflammation. At 12 weeks postinfection, there was evidence of less pathology, and of clearing of abscesses. In contrast to the pathology produced by 0.1 X 10(7) P. brasiliensis in young mice, no pathology evident on gross examination was produced by a similar dose in adult mice. Immunological evaluations of mice with chronic pulmonary-disseminated disease showed that spleen cells, but not lymph node cells, had significantly depressed blastogenic responses to concanavalin A (ConA) early after infection. However, at 12 weeks postinfection, when pathological examination indicated beginning resolution of infection, spleen cell responses to ConA were normal. The model of chronic disease is of interest for further immunological studies as well.