Candida albicans and Candida krusei differentially induce human blood mononuclear cell interleukin-12 and gamma interferon production

Protection against Candida infection involves bath innate and acquired immu ne responses, and cytokines produced by monocytes during the innate respons e may modify the acquired immune response by T cells. We hypothesized that Candida species which differ in pathogenicity can differentially induce pro duction of immunoregulatory cytokines by human monocytes, which in turn mod ify T cells for immune responses to Candida. To test this hypothesis, we ex amined the effects of Candida albicans and Candida krusei on immunoregulato ry cytokine production by human monocytes and gamma interferon (IFN-gamma) production by peripheral blood mononuclear cells (PBMC). Purified monocytes were incubated with live or heat-killed strains of C. albicans and C. krus ei at the optimal Candida/monocyte ratio of 0.5. Cytokines in the supernata nts were measured by enzyme-linked immunosorbent assay. Our data demonstrat ed that live C. albicans and C. krusei significantly induced interleukin-10 (IL-10), monocyte chemotactic factor 1, IL-1 beta, and tumor necrosis fact or alpha production by monocytes relative to unstimulated monocytes. In con trast, unlike C. krusei, pathogenic live strains of C. albicans induced no or only a minimal level of IL-12. The expression of IL-12 p40 mRNA levels b y reverse transcription-PCR corroborated the IL-12 protein (p70) findings. In human PBMC, human blood monocytes were the major source of both IL-10 an d IL-12 production in response to C. albicans and C. krusei. Upon activatio n of T cells in the presence of Candida-modified monocytes and antigen-pres enting cells, IL-12 production by PBMC treated with Candida organisms corre lated strongly with the level of IFN-gamma production by T cells. These res ults indicate that the virulence of C. albicans may. be related to its abil ity to induce the monocytic type II cytokine IL-10, with a selective inhibi tion of IL-12 production, which may be responsible for the observed lack of T-cell IFN-gamma and may restrain an effective type I immune response to C andida.