Candida albicansandCandida kruseiDifferentially Induce Human Blood Mononuclear Cell Interleukin-12 and Gamma Interferon Production

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Abstract
Protection againstCandidainfection involves both innate and acquired immune responses, and cytokines produced by monocytes during the innate response may modify the acquired immune response by T cells. We hypothesized thatCandidaspecies which differ in pathogenicity can differentially induce production of immunoregulatory cytokines by human monocytes, which in turn modify T cells for immune responses toCandida. To test this hypothesis, we examined the effects ofCandida albicansandCandida kruseion immunoregulatory cytokine production by human monocytes and gamma interferon (IFN-γ) production by peripheral blood mononuclear cells (PBMC). Purified monocytes were incubated with live or heat-killed strains ofC. albicansandC. kruseiat the optimalCandida/monocyte ratio of 0.5. Cytokines in the supernatants were measured by enzyme-linked immunosorbent assay. Our data demonstrated that liveC. albicansandC. kruseisignificantly induced interleukin-10 (IL-10), monocyte chemotactic factor 1, IL-1β, and tumor necrosis factor alpha production by monocytes relative to unstimulated monocytes. In contrast, unlikeC. krusei, pathogenic live strains ofC. albicansinduced no or only a minimal level of IL-12. The expression of IL-12 p40 mRNA levels by reverse transcription-PCR corroborated the IL-12 protein (p70) findings. In human PBMC, human blood monocytes were the major source of both IL-10 and IL-12 production in response toC. albicansandC. krusei. Upon activation of T cells in the presence ofCandida-modified monocytes and antigen-presenting cells, IL-12 production by PBMC treated withCandidaorganisms correlated strongly with the level of IFN-γ production by T cells. These results indicate that the virulence ofC. albicansmay be related to its ability to induce the monocytic type II cytokine IL-10, with a selective inhibition of IL-12 production, which may be responsible for the observed lack of T-cell IFN-γ and may restrain an effective type I immune response toCandida.