Evolution of inflammatory response and cellular immune responses in a murine model of disseminated blastomycosis.
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.
D000818:Animals; D000917:Antibody Formation; D001758:Blastomyces / Q000472:pathogenicity; D001759:Blastomycosis / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D001921:Brain / Q000382:microbiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007958:Leukocyte Count; D008168:Lung / Q000382:microbiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D013997:Time Factors