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Journal Article

Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons82192

Urban,  Constantin F.
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81869

Ermert,  David
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82139

Schmid,  Monika
Core Facilities / Proteinanalysis, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81777

Abu-Abed,  Ulrike
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Max Planck Society;
Core Facilities / Microscopy, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81900

Goosmann,  Christian
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Max Planck Society;
Core Facilities / Microscopy, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81827

Brinkmann,  Volker
Core Facilities / Microscopy, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81959

Jungblut,  Peter R.
Core Facilities / Proteinanalysis, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82241

Zychlinsky,  Arturo
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Max Planck Society;

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Fulltext (public)

PLoS_Pathogens_2009_5_e1000639.pdf
(Publisher version), 2MB

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Citation

Urban, C. F., Ermert, D., Schmid, M., Abu-Abed, U., Goosmann, C., Nacken, W., et al. (2009). Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans. PLoS Pathogens, 5(10): e1000639.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-C08B-0
Abstract
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.