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Infection and Immunity, December 2009, p. 5216-5224, Vol. 77, No. 12
0019-9567/09/$08.00+0 doi:10.1128/IAI.00723-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

University of Würzburg, Institute of Hygiene and Microbiology, Würzburg, Germany,1 University of Würzburg, Department of Internal Medicine II, Würzburg, Germany,2 Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knoell Institute, Jena, Germany,3 Friedrich-Schiller University, Jena, Germany4
Received 26 June 2009/ Returned for modification 29 July 2009/ Accepted 25 September 2009
Human polymorphonuclear neutrophils (PMNs) play a major role in the immune defense against invasive Candida albicans infection. This fungal pathogen produces a set of aspartic proteases that directly contributes to virulence properties such as adhesion, tissue invasion, and immune evasion. We show here that, in contrast to other secreted proteases, the cell surface-associated isoform Sap9 has a major impact on the recognition of C. albicans by PMNs. SAP9 is required for the induction of PMN chemotaxis toward C. albicans filaments, an essential prerequisite of effective PMN activation. Furthermore, deletion of SAP9 leads to a mitigated release of reactive oxygen intermediates (ROI) in human PMNs and decreases C. albicans-induced apoptosis triggered by ROI formation. In confrontation assays, killing of a SAP9 deletion mutant is reduced in comparison to wild-type C. albicans. These data clearly implicate Sap9 protease activity in the initiation of protective innate immunity and suggest novel molecular mechanisms in C. albicans-host interaction leading to neutrophil activation.
Published ahead of print on 5 October 2009.
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