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

Abstract

The pathogenic fungusCandida albicansis able to cover its most potent proinflammatory cell wall molecules, theβ-glucans, underneath a dense mannan layer, so that the pathogen becomes partly invisible for immune cells such as phagocytes. As theC. albicanshistidine 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 againstC. albicans. We found that among all histidine kinase genes,CHK1plays a prominent role in phagocyte activation. Uptake of the deletion mutant Δchk1as well as the acidification of Δchk1-carrying phagosomes was significantly increased compared with the parental strain. These improved activities could be correlated with an enhanced accessibility of the mutantβ-1,3-glucans for immunolabelling. In addition, any inhibition ofβ-1,3-glucan-mediated phagocytosis resulted in a reduced uptake of Δchk1, while ingestion of the parental strain was hardly affected. Moreover, deletion ofCHK1caused an enhanced release of interleukins 6 and 10, indicating a stronger activation of theβ-1,3-glucan receptor dectin-1. In conclusion, the Chk1p protein is likely to be involved in maskingβ-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.