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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...

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Autores principales: Halder, Luke D., Abdelfatah, Mahmoud A., Jo, Emeraldo A. H., Jacobsen, Ilse D., Westermann, Martin, Beyersdorf, Niklas, Lorkowski, Stefan, Zipfel, Peter F., Skerka, Christine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
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.
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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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