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Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans
Upon systemic infection with human pathogenic yeast Candida albicans (C. albicans), human monocytes and polymorph nuclear neutrophilic granulocytes are the first immune cells to respond and come into contact with C. albicans. Monocytes exert immediate candidacidal activity and inhibit germination, m...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233719/ https://www.ncbi.nlm.nih.gov/pubmed/28133459 http://dx.doi.org/10.3389/fimmu.2016.00671 |
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author | Halder, Luke D. Abdelfatah, Mahmoud A. Jo, Emeraldo A. H. Jacobsen, Ilse D. Westermann, Martin Beyersdorf, Niklas Lorkowski, Stefan Zipfel, Peter F. Skerka, Christine |
author_facet | Halder, Luke D. Abdelfatah, Mahmoud A. Jo, Emeraldo A. H. Jacobsen, Ilse D. Westermann, Martin Beyersdorf, Niklas Lorkowski, Stefan Zipfel, Peter F. Skerka, Christine |
author_sort | Halder, Luke D. |
collection | PubMed |
description | Upon systemic infection with human pathogenic yeast Candida albicans (C. albicans), human monocytes and polymorph nuclear neutrophilic granulocytes are the first immune cells to respond and come into contact with C. albicans. Monocytes exert immediate candidacidal activity and inhibit germination, mediate phagocytosis, and kill fungal cells. Here, we show that human monocytes spontaneously respond to C. albicans cells via phagocytosis, decondensation of nuclear DNA, and release of this decondensed DNA in the form of extracellular traps (called monocytic extracellular traps: MoETs). Both subtypes of monocytes (CD14(++)CD16(−)/CD14(+)CD16(+)) formed MoETs within the first hours upon contact with C. albicans. MoETs were characterized by the presence of citrullinated histone, myeloperoxidase, lactoferrin, and elastase. MoETs were also formed in response to Staphylococcus aureus and Escherichia coli, indicating a general reaction of monocytes to infectious microbes. MoET induction differs from extracellular trap formation in macrophages as MoETs are not triggered by simvastatin, an inhibitor of cholesterol synthesis and inducer of extracellular traps in macrophages. Extracellular traps from both monocytes and neutrophils activate complement and C3b is deposited. However, factor H (FH) binds via C3b to the extracellular DNA, mediates cofactor activity, and inhibits the induction of the inflammatory cytokine interleukin-1 beta in monocytes. Altogether, the results show that human monocytes release extracellular DNA traps in response to C. albicans and that these traps finally bind FH via C3b to presumably support clearance without further inflammation. |
format | Online Article Text |
id | pubmed-5233719 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-52337192017-01-27 Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans Halder, Luke D. Abdelfatah, Mahmoud A. Jo, Emeraldo A. H. Jacobsen, Ilse D. Westermann, Martin Beyersdorf, Niklas Lorkowski, Stefan Zipfel, Peter F. Skerka, Christine Front Immunol Immunology Upon systemic infection with human pathogenic yeast Candida albicans (C. albicans), human monocytes and polymorph nuclear neutrophilic granulocytes are the first immune cells to respond and come into contact with C. albicans. Monocytes exert immediate candidacidal activity and inhibit germination, mediate phagocytosis, and kill fungal cells. Here, we show that human monocytes spontaneously respond to C. albicans cells via phagocytosis, decondensation of nuclear DNA, and release of this decondensed DNA in the form of extracellular traps (called monocytic extracellular traps: MoETs). Both subtypes of monocytes (CD14(++)CD16(−)/CD14(+)CD16(+)) formed MoETs within the first hours upon contact with C. albicans. MoETs were characterized by the presence of citrullinated histone, myeloperoxidase, lactoferrin, and elastase. MoETs were also formed in response to Staphylococcus aureus and Escherichia coli, indicating a general reaction of monocytes to infectious microbes. MoET induction differs from extracellular trap formation in macrophages as MoETs are not triggered by simvastatin, an inhibitor of cholesterol synthesis and inducer of extracellular traps in macrophages. Extracellular traps from both monocytes and neutrophils activate complement and C3b is deposited. However, factor H (FH) binds via C3b to the extracellular DNA, mediates cofactor activity, and inhibits the induction of the inflammatory cytokine interleukin-1 beta in monocytes. Altogether, the results show that human monocytes release extracellular DNA traps in response to C. albicans and that these traps finally bind FH via C3b to presumably support clearance without further inflammation. Frontiers Media S.A. 2017-01-13 /pmc/articles/PMC5233719/ /pubmed/28133459 http://dx.doi.org/10.3389/fimmu.2016.00671 Text en Copyright © 2017 Halder, Abdelfatah, Jo, Jacobsen, Westermann, Beyersdorf, Lorkowski, Zipfel and Skerka. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Halder, Luke D. Abdelfatah, Mahmoud A. Jo, Emeraldo A. H. Jacobsen, Ilse D. Westermann, Martin Beyersdorf, Niklas Lorkowski, Stefan Zipfel, Peter F. Skerka, Christine Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans |
title | Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans |
title_full | Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans |
title_fullStr | Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans |
title_full_unstemmed | Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans |
title_short | Factor H Binds to Extracellular DNA Traps Released from Human Blood Monocytes in Response to Candida albicans |
title_sort | factor h binds to extracellular dna traps released from human blood monocytes in response to candida albicans |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233719/ https://www.ncbi.nlm.nih.gov/pubmed/28133459 http://dx.doi.org/10.3389/fimmu.2016.00671 |
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