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  - 
TY  - JOUR
A1  - Silva-Vilches, Cinthia
A1  - Pletinckx, Katrien
A1  - Lohnert, Miriam
A1  - Pavlovic, Vladimir
A1  - Ashour, Diyaaeldin
A1  - John, Vini
A1  - Vendelova, Emilia
A1  - Kneitz, Susanne
A1  - Zhou, Jie
A1  - Chen, Rena
A1  - Reinheckel, Thomas
A1  - Mueller, Thomas D.
A1  - Bodem, Jochen
A1  - Lutz, Manfred B.
T1  - Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion
JF  - PLoS ONE
N2  - Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.
KW  - small interfering RNAs
KW  - toxins
KW  - regulatory T cells
KW  - T cells
KW  - cytokines
KW  - cholera
KW  - cell differentiation
KW  - immune evasion
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158244
VL  - 12
IS  - 7
ER  -