Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.

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 microb...

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Autores principales:	Constantin F Urban, David Ermert, Monika Schmid, Ulrike Abu-Abed, Christian Goosmann, Wolfgang Nacken, Volker Brinkmann, Peter R Jungblut, Arturo Zychlinsky
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/b0fa61adc9e5401ca66318cc3ea067f4
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spelling	oai:doaj.org-article:b0fa61adc9e5401ca66318cc3ea067f42021-11-25T05:48:32ZNeutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.1553-73661553-737410.1371/journal.ppat.1000639https://doaj.org/article/b0fa61adc9e5401ca66318cc3ea067f42009-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19876394/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Neutrophils 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.Constantin F UrbanDavid ErmertMonika SchmidUlrike Abu-AbedChristian GoosmannWolfgang NackenVolker BrinkmannPeter R JungblutArturo ZychlinskyPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 10, p e1000639 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Constantin F Urban David Ermert Monika Schmid Ulrike Abu-Abed Christian Goosmann Wolfgang Nacken Volker Brinkmann Peter R Jungblut Arturo Zychlinsky Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
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.
format	article
author	Constantin F Urban David Ermert Monika Schmid Ulrike Abu-Abed Christian Goosmann Wolfgang Nacken Volker Brinkmann Peter R Jungblut Arturo Zychlinsky
author_facet	Constantin F Urban David Ermert Monika Schmid Ulrike Abu-Abed Christian Goosmann Wolfgang Nacken Volker Brinkmann Peter R Jungblut Arturo Zychlinsky
author_sort	Constantin F Urban
title	Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
title_short	Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
title_full	Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
title_fullStr	Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
title_full_unstemmed	Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.
title_sort	neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against candida albicans.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/b0fa61adc9e5401ca66318cc3ea067f4
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Neutrophil extracellular traps contain calprotectin, a cytosolic protein complex involved in host defense against Candida albicans.

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