1887

Abstract

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

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2010-11-01
2020-10-20
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