TY  - JOUR
A1  - Halder, Luke D.
A1  - Abdelfatah, Mahmoud A.
A1  - Jo, Emeraldo A. H.
A1  - Jacobsen, Ilse D.
A1  - Westermann, Martin
A1  - Beyersdorf, Niklas
A1  - Lorkowski, Stefan
A1  - Zipfel, Peter F.
A1  - Skerka, Christine
T1  - Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans
JF  - Frontiers in Immunology
N2  - 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.
KW  - Candida
KW  - monocytes
KW  - DNA traps
KW  - MPO
KW  - factor H
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181127
VL  - 7
ER  - 
TY  - JOUR
A1  - Bergfeld, Arne
A1  - Dasari, Prasad
A1  - Werner, Sandra
A1  - Hughes, Timothy R.
A1  - Song, Wen-Chao
A1  - Hortschansky, Peter
A1  - Brakhage, Axel A.
A1  - Hünig, Thomas
A1  - Zipfel, Peter F.
A1  - Beyersdorf, Niklas
T1  - Direct binding of the pH-regulated Protein 1 (Pra1) from Candida albicans inhibits cytokine secretion by mouse CD4\(^{+}\) T cells
JF  - Frontiers in Microbiology
N2  - Opportunistic infections with the saprophytic yeast Candida albicans are a major cause of morbidity in immunocompromised patients. While the interaction of cells and molecules of innate immunity with C. albicans has been studied to great depth, comparatively little is known about the modulation of adaptive immunity by C. albicans. In particular, direct interaction of proteins secreted by C. albicans with CD4\(^{+}\) T cells has not been studied in detail. In a first screening approach, we identified the pH-regulated antigen 1 (Pra1) as a molecule capable of directly binding to mouse CD4\(^{+}\) T cells in vitro. Binding of Pra1 to the T cell surface was enhanced by extracellular Zn\(^{2+}\) ions which Pra1 is known to scavenge from the host in order to supply the fungus with Zn\(^{2+}\). In vitro stimulation assays using highly purified mouse CD4\(^{+}\) T cells showed that Pra1 increased proliferation of CD4\(^{+}\) T cells in the presence of plate-bound anti-CD3 monoclonal antibody. In contrast, secretion of effector cytokines such as IFNγ and TNF by CD4\(^{+}\) T cells upon anti-CD3/ anti-CD28 mAb as well as cognate antigen stimulation was reduced in the presence of Pra1. By secreting Pra1 C. albicans, thus, directly modulates and partially controls CD4\(^{+}\) T cell responses as shown in our in vitro assays.
KW  - Candida albicans
KW  - pH-regulated antigen 1 (Pra1)
KW  - CD4\(^{+}\) T cells
KW  - immune evasion
KW  - cytokine secretion
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158274
VL  - 8
IS  - 844
ER  -