In vitro pro- and anti-inflammatory responses to viable Candida albicans yeasts by a murine macrophage cell line.

The balance between pro- and anti-inflammatory cytokine production is a crucial aspect of infections caused by Candida albicans. We therefore investigated the effect of yeast concentration on the pro- and anti-inflammatory cytokine response. Production of tumor necrosis factor-alpha (TNF-α) by the murine macrophage cell line J774 decreased significantly as the live yeast concentration increased. In parallel, a dose-dependent production of interleukin-10 (IL-10) was observed with live C. albicans. Paraformaldehyde-treated yeasts were unable to stimulate or modulate this response. Yeast culture supernatants induced high levels of TNF-α production when added to the macrophage cells, but did not down-modulate the macrophage response. In contrast, supernatants from yeast-macrophage co-cultures stimulated less TNF-α production and induced a down-modulation of the macrophage response, showing that modulation depended on macrophage- or yeast-derived components secreted when the yeast concentration was high. Phospholipomannan (PLM), but not farnesol, stimulated TNF-α production, but neither PLM nor farnesol down-modulated cytokine production in response to yeasts. Yeast culture supernatants or supernatants from yeast-macrophage co-cultures did not induce IL-10 production. These results suggest that the final macrophage cytokine response is determined by the interplay between live yeasts and macrophages, and that the direction of the response is dependent on the yeast concentration.