| Summary: | <p>Abstract</p> <p>Background</p> <p>We have previously shown that supernatant from <it>Candida albicans </it>(CA) culture contains a Secretory Interleukin (IL)-12 Inhibitory Factor (CA-SIIF), which inhibits IL-12 production by human monocytes. However, the effect of CA-SIIF on secretion of other cytokines by monocytes is unknown, and detailed characterization of this factor has not been performed.</p> <p>Results</p> <p>In this study, we demonstrate that the IL-12 inhibitory activity of CA-SIIF was serum-independent, based on the reduction of IL-12 levels in monocytes stimulated under serum-independent conditions. The minimal inhibitory dose of CA-SIIF was found to be 200 μg/ml. Investigation of CA-SIIF's effect on macrophages IL-12 production <it>in vitro </it>and <it>in vivo </it>also showed that CA-SIIF inhibited IL-12 production by murine macrophages both <it>in vitro </it>(from 571 ± 24 pg/ml to 387 ± 87 pg/ml; P = 0.05) and <it>in vivo </it>(from 262 ± 6 pg/ml to 144 ± 30 pg/ml; <it>P </it>< 0.05). In addition to IL-12, cytokine array analysis revealed that CA-SIIF induced differential production of other cytokines also. In this regard, reduction in levels were observed for IL-8, IL-10, IL-13, monocyte chemoattractant protein (MCP)-1, MCP-2, macrophage inflammatory protein (MIP)-1, RANTES, etc. In contrast, levels of other chemokines e.g. MCP-4, MIF and MIP-3α (<it>P </it>< 0.05) were increased. We also found that CA-SIIF suppressed the maturation of human monocytes to dendritic cells (CD1a expression = 13 ± 3% vs 36 ± 2% of the control; <it>P </it>< 0.01). Next, to identify the biochemical nature of CA-SIIF, we separated this factor into a Concanavalin A (ConA)-binding glycoprotein fraction (CA-SIIF-GP) and a non-ConA-binding protein fraction (CA-SIIF-NGP) using ConA affinity chromatography. Both fractions were then tested for this inhibitory effect on human monocyte IL-12 production. CA-SIIF-GP produced a higher inhibitory effect on IL-12 production compared to CA-SIIF-NGP and CA-SIIF crude (<it>P </it>< 0.01), proving that CA-SIIF is a glycoprotein in nature.</p> <p>Conclusion</p> <p>CA-SIIF is a glycoprotein which exhibits serum-independent inhibition of IL-12 production from monocytes <it>in vitro </it>and <it>in vivo</it>, and also modulates differentiation of monocytes into dendritic cells. These results suggest important role for CA-SIIF in interactions of <it>C. albicans </it>with the host immune system.</p>
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