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

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Urban, Constantin F., Ermert, David, Schmid, Monika, Abu-Abed, Ulrike, Goosmann, Christian, Nacken, Wolfgang, Brinkmann, Volker, Jungblut, Peter R., Zychlinsky, Arturo·2009·PLoS Pathogens
DOI 10.1371/journal.ppat.1000639
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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.

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Metadata

Authors
Urban, C. F., Ermert, D., Schmid, M., Abu-Abed, U., Goosmann, C., Nacken, W., Brinkmann, V., Jungblut, P. R., & Zychlinsky, A.
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2009-10-30
Volume
5
Issue
10
Pages
e1000639
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1000639
OpenAlex
W2169535061
Cited by
1,673
References
7
FWCI
16.80
Type
journal article
Language
en
Open access
gold
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans. https://app.cochat.ai/papers/10.1371/journal.ppat.1000639
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Urban, C. F., Ermert, D., Schmid, M., Abu-Abed, U., Goosmann, C., Nacken, W., Brinkmann, V., Jungblut, P. R., & Zychlinsky, A. (2009). Neutrophil Extracellular Traps Contain Calprotectin, a Cytosolic Protein Complex Involved in Host Defense against Candida albicans. PLoS Pathogens. https://doi.org/10.1371/journal.ppat.1000639

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