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A reproducible model of disseminated blastomycosis was established in C57BL/6 mice by intravenous injection of 10(6) yeast-phase Blastomyces dermatiditis organisms. The infection progressed over 5 weeks to involve lungs, brains, superficial fascia, livers, and spleens of mice. By week 5, there was a greater number of organisms in lungs and brains than in livers and spleens. The tissue response in lungs, brains, and livers progressed from acute neutrophilic invasion before week 1 to pyogranuloma formation by week 5. Lymph nodes and spleens were remarkably spared. By week 5, infected mice became anergic to intradermal challenge with both specific Blastomyces antigen and a nonspecific antigen (sheep erythrocytes). At this time, the response to concanavalin A or phytohemagglutinin by splenocytes was markedly less than that of normal controls. Likewise, the plaque-forming cell response to sheep erythrocytes by splenocytes from infected mice was diminished. In coculture studies, splenocytes from 5-week-infected mice reduced the plaque-forming cell response by normal splenocytes. The development of this murine model should prove useful for elucidating the perturbations of immunoregulation associated with disseminated blastomycosis.

Evolution of inflammatory response and cellular immune responses in a murine model of disseminated blastomycosis