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          Institute: MPI für Infektionsbiologie     Collection: Core Facilites     Display Documents



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ID: 572808.0, MPI für Infektionsbiologie / Core Facilites
Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans
Authors:Urban, Constantin F.; Ermert, David; Schmid, Monika; Abu-Abed, Ulrike; Goosmann, Christian; Nacken, Wolfgang; Brinkmann, Volker; Jungblut, Peter R.; Zychlinsky, Arturo
Language:English
Date of Publication (YYYY-MM-DD):2009-10
Title of Journal:PLoS Pathogens
Volume:5
Issue / Number:10
Sequence Number of Article:e1000639
Copyright:© 2009 Urban et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Neutrophils are the first line of defense at the site of an infection. They encounter and kill microbes intracellularly upon phagocytosis or extracellularly by degranulation of antimicrobial proteins and the release of Neutrophil Extracellular Traps (NETs). NETs were shown to ensnare and kill microbes. However, their complete protein composition and the antimicrobial mechanism are not well understood. Using a proteomic approach, we identified 24 NET-associated proteins. Quantitative analysis of these proteins and high resolution electron microscopy showed that NETs consist of modified nucleosomes and a stringent selection of other proteins. In contrast to previous results, we found several NET proteins that are cytoplasmic in unstimulated neutrophils. We demonstrated that of those proteins, the antimicrobial heterodimer calprotectin is released in NETs as the major antifungal component. Absence of calprotectin in NETs resulted in complete loss of antifungal activity in vitro. Analysis of three different Candida albicans in vivo infection models indicated that NET formation is a hitherto unrecognized route of calprotectin release. By comparing wild-type and calprotectin-deficient animals we found that calprotectin is crucial for the clearance of infection. Taken together, the present investigations confirmed the antifungal activity of calprotectin in vitro and, moreover, demonstrated that it contributes to effective host defense against C. albicans in vivo. We showed for the first time that a proportion of calprotectin is bound to NETs in vitro and in vivo.
External Publication Status:published
Document Type:Article
Communicated by:Beate Löhr
Affiliations:MPI für Infektionsbiologie/Department of Cellular Microbiology
MPI für Infektionsbiologie/Core Facilities
External Affiliations:Institute for Immunology, Münster University, Münster, Germany; Institute for Molecular Virology, Center for Molecular Biology of Inflammation, Münster University, Münster, Germany.
Identifiers:ISI:000272033300043 [ID No:1]
ISSN:1553-7366 [ID No:2]
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