Interaction of chemotherapy and immune defenses in experimental murine cryptococcosis.
Congenitally athymic nude (nu/nu) and thymus-containing heterozygous (nu/X) mice were infected intraperitoneally with Cryptococcus neoformans over a wide range of challenge doses. Cryptococcal disease progressed more rapidly in nude mice than in their nu/X littermates. When nu/X mice were treated with amphotericin B, all survived an otherwise lethal dose of C. neoformans. At larger challenge doses, survival was prolonged in nu/nu mice treated with amphotericin B, but they later succumbed to cryptococcosis. At lower challenge doses, amphotericin B was curative in some nude mice. Therapy of nude mice with both amphotericin B and flucytosine further prolonged survival at high-dose challenge and increased the number of cures at low-dose challenge. These studies support an interaction of antifungal chemotherapy with thymus-dependent immune defense mechanisms. This interaction is most evident at high challenge doses, where antifungal chemotherapy cures nu/X mice but only modestly prolongs survival in nude mice.
D000666:Amphotericin B / Q000097:blood / Q000627:therapeutic use; D000818:Animals; D003453:Cryptococcosis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000187:drug effects; D005260:Female; D005437:Flucytosine / Q000097:blood / Q000627:therapeutic use; D007111:Immunity, Cellular / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008826:Microbial Sensitivity Tests
D000666:Amphotericin B; D005437:Flucytosine