Deletion of the Candida albicans histidine kinase gene CHK1 improves recognition by phagocytes through an increased exposure of cell wall β-1,3-glucans

The pathogenic fungus Candida albicans is able to cover its most potent proinflammatory cell wall molecules, the beta-glucans, underneath a dense mannan layer, so that the pathogen becomes partly invisible for immune cells such as phagocytes. As the C. albicans histidine kinases Chk1p, Cos1p and CaSln1p had been reported to be involved in virulence and cell wall biosynthesis, we investigated whether deletion of the respective genes influences the activity of phagocytes against C. albicans. We found that among all histidine kinase genes, CHK1 plays a prominent role in phagocyte activation. Uptake of the deletion mutant Delta chk1 as well as the acidification of Delta chk1-carrying phagosomes was significantly increased compared with the parental strain. These improved activities could be correlated with an enhanced accessibility of the mutant beta-1,3-glucans for immunolabelling. In addition, any inhibition of beta-1,3-glucan-mediated phagocytosis resulted in a reduced uptake of Delta chk1, while ingestion of the parental strain was hardly affected. Moreover, deletion of CHK1 caused an enhanced release of interleukins 6 and 10, indicating a stronger activation of the beta-1,3-glucan receptor dectin-1. In conclusion, the Chk1p protein is likely to be involved in masking beta-1,3-glucans from immune recognition. As there are no homologues of fungal histidine kinases in mammals, Chk1p has to be considered as a promising target for new antifungal agents.