Candida albicans is an important nosocomial pathogen. Monocytes are important in host defense against this organism. One monocyte contribution to host defense is the elaboration of chemotactic factors such as IL-8, which recruit neutrophils to the site of infection. We sought to evaluate the monocyte IL-8 response to C. albicans. Mononuclear cells were isolated from peripheral blood, monocytes were allowed to adhere in 24 well tissue culture plates (106/ml) and lymphocytes were washed off. The C. albicans used was isolated from a premature neonate with systemic candidiasis. The yeast were diluted in monocyte media (RPMI with L-glutamine, 25 mM HEPES, 1 mM pyruvate, 50 μg/ml gentamicin and 1% Nutridoma-HU); colony counts were determined spectrophotometrically by comparison with a standard curve and verified by serial dilutions. The yeast were added to the monocytes at time 0; supernatants were harvested at 24h, filtered and frozen at -70°C until assayed. IL-8 was determined by ELISA (R&D Systems, Minneapolis, MN). In initial experiments, we attempted to generate a dose response curve to live C. albicans from 104 to 108 CFU/ml. Surprisingly, at all concentrations the amount of IL-8 released was similar to that released by adherent cells without additional stimulus. We hypothesized that growing yeast suppress the inflammatory response. To test this hypothesis, we compared the IL-8 response elicited by 108 heat-killed C. albicans versus live yeast. As seen in the table below, IL-8 release by monocytes in response to heat-killed yeast was significantly (ANOVA, p<.05, n=3) greater than in response to the live C. albicans. When tested by ANOVA, the IL-8 response to live yeast was not different from the amount released by unstimulated monocytes. In conclusion, live C. albicans do not elicit significant amounts of IL-8 whereas heat-killed yeasts do. We propose that this contributes to the virulence of this pathogen, limiting the recruitment of neutrophils to the site of infection. As the mannan components of C. albicans are known to have immunomodulatory effects, we speculate that these components are responsible for the diminished IL-8 response to living yeasts.

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