Immunomodulation by a low-virulence, agerminative variant of Candida albicans. Further evidence for macrophage activation as one of the effector mechanisms of nonspecific anti-infectious protection.
Systemic infection of mice with a Candida albicans strain (PCA-2) incapable of yeast-mycelial conversion is known to activate host macrophages and confer protection against subsequent challenge with highly pathogenic cells of the same species or by other micro-organisms. In an attempt to define the relative contributions of different immune components to the protection mediated by PCA-2, we evaluated the effect of manipulations known to selectively deplete immune functions. By means of cytostatic drug or silica induced toxicity, it was possible to demonstrate that no crucial role in protection is played by cytotoxic T lymphocytes or B cells, nor by PCA-2 induced granulocytosis alone. The cells responsible for this effect were dacarbazine-resistant silica-sensitive macrophages whose activity in vivo paralleled the in vitro expression of splenic candidacidal activity. Macrophage activation by PCA-2 and increased anti-Candida resistance did not result from an immunological response mediated by T-dependent effectors, as these effects could be reproduced in athymic mice.
Bistoni
F
F
Department of Experimental Medicine, University of Perugia, Via del Giochetto, Perugia, Italy.
Verducci
G
G
Perito
S
S
Vecchiarelli
A
A
Puccetti
P
P
Marconi
P
P
Cassone
A
A
D000276:Adjuvants, Immunologic; D000818:Animals; D000908:Antibodies, Fungal / Q000096:biosynthesis; D002176:Candida albicans / Q000187:drug effects / Q000276:immunology*; D002177:Candidiasis / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D003606:Dacarbazine / Q000494:pharmacology; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007958:Leukocyte Count / Q000187:drug effects; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012822:Silicon Dioxide / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000908:Antibodies, Fungal; D012822:Silicon Dioxide; D003606:Dacarbazine