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  - Dühring, Sybille
A1  - Germerodt, Sebastian
A1  - Skerka, Christine
A1  - Zipfel, Peter F.
A1  - Dandekar, Thomas
A1  - Schuster, Stefan
T1  - Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies
JF  - Frontiers in Microbiology
N2  - The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.
KW  - agent-based model
KW  - antimicrobial peptides
KW  - fungal pathogens
KW  - Candida albicans
KW  - immunological cross-talk
KW  - beta-lactamase inhibition
KW  - in vitro
KW  - biomaterial surfaces
KW  - biofilm formation
KW  - dendritic cells
KW  - infection
KW  - resistance
KW  - human immune system
KW  - host-pathogen interaction
KW  - computational systems biology
KW  - defense and evasion strategies
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151621
VL  - 6
IS  - 625
ER  -