Strain differences in the severity of lesions in murine systemic candidiasis correlate with the production of functional gamma interferon by Candida-activated lymphocytes in vitro.

Abstract

BALB/c mice exhibit mild, and CBA/CaH mice exhibit severe tissue lesions after systemic infection with the yeast Candida albicans. There is considerable evidence that recovery from primary infection is associated with the development of cell-mediated immune responses in the infected mice, and that cytokines produced by T lymphocytes augment the phagocytic and candidacidal functions of macrophages and polymorphonuclear leukocytes. To determine whether the severity of lesions in the two inbred strains was associated with differences in cytokine production, lymphocytes were obtained from the spleens of normal and immune mice, activated with Candida antigens in vitro, and functional cytokines identified by bioassay. mRNA obtained from the activated lymphocytes was also screened for cytokine-specific sequences by S1-nuclease protection analysis. mRNA for IL-3 and IFN-gamma, but not IL-2 or IL-4, was detected in lymphocytes from both BALB/c and CBA/CaH mice, but only lymphocytes from primary and secondary cultures of BALB/c cells showed Candida-specific induction of IFN-gamma bioactivity. These results suggest that, in this murine model of systemic candidiasis, the propensity to develop severe lesions exhibited by CBA/CaH mice may be a consequence of some form of posttranscriptional regulation of gamma-interferon production.