Protective immunity induced by low-virulence Candida albicans: cytokine production in the development of the anti-infectious state.

A low-virulence, agerminative strain of Candida albicans (PCA-2) is able to confer a high degree of nonspecific protection against subsequent challenge with highly virulent microorganisms in mice. In an attempt to better define the effect of PCA-2 vaccination on the immune system and the nature of the mechanisms involved in this protective state, we evaluated the pattern and kinetics of production of selected cytokines in PCA-2-treated mice. Thus, granulocyte/monocyte colony-stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 1 (IL-1) were measured in the sera and spleen cell supernatants of vaccinated mice. In both cases, high levels of CSF, TNF, IL-1, and IFN were found 6 hr after PCA-2 infection and persisted for many days. There was always a correlation between the ability of PCA-2 to induce antimicrobial protection in vivo and its ability to cause cytokine production in vitro. Supernatants of splenocyte cultures from PCA-2-infected animals possessed macrophage-activating activity, as measured in microbiological assays. These data suggest an important involvement of cytokines in the nonspecific anti-infectious immunity induced by PCA-2, and also suggest a crucial role for IL-1 as an endogenous adjuvant in the initiation of the immune response to PCA-2.