Project C6

Project Description

Candida albicans is an important human pathogen, which interferes with both innate and adaptive immune responses of the human host. While the modulation of innate immune responses by C. albicans has already been studied to some depth very little is known about how the fungus acts on T cells. Therefore, we are planning to screen the C. albicans secretome for proteins that bind to human and mouse T cells and modulate their function in vitro. As a proof of concept, we have already identified the pH-regulated antigen 1 (Pra1) of C. albicans as a modulator of T cell function. On the proteins identified upon screening we will perform an extensive biochemical analysis including the identification of their binding partners on the surface of T cells. The mouse system, further, allows us to study the impact of fungal proteins on T cell responses to nominal antigen in vivo. Moreover, we will generate monoclonal antibodies (mAb) against the candidate proteins as a tool for further characterisation of the proteins and which we will test for their therapeutic efficacy in a C. albicans infection model in mice.

Principal Investigators

Dr. Niklas Beyersdorf
PD Dr. Niklas Beyersdorf

Institute for Virology and Immunobiology and Research Center for Infectious Diseases (ZINF)
 
Julius Maximilians University Würzburg

niklas.beyersdorf@vim.uni-wuerzburg.de

 

Prof. Dr. Peter F. Zipfel
Prof. Dr. Peter F. Zipfel

Department of Infection Biology 

Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute  

peter.zipfel@leibniz-hki.de

Publications

Author Year Title Journal Links

Dühring S, Germerodt S, Skerka C, Zipfel PF, Dandekar T, Schuster S

2015

Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies.

Front Microbiol 6: 625

Frontiers
Zipfel PF, Skerka C 2014 Staphylococcus aureus: the multi headed hydra resists and controls human complement response in multiple ways. Int J Med Microbio 304: 188-94 PubMed
Luo S, Hipler UC, Münzberg C, Skerka C, Zipfel PF 2015 Sequence variations and protein expression levels of the two immune evasion proteins Gpm1 and Pra1 influence virulence of clinical Candida albicans isolates. PLoS One 10: e0113192 PubMed
Pollmächer J, Timme S, Schuster S, Brakhage AA, Zipfel PF, Figge MT 2016 Deciphering the counterplay of Aspergillus fumigatus infection and host inflammation by evolutionary games on graphs.

Sci Rep 6: 27807

PubMed
Buhlmann D, Eberhardt HU, Medyukhina A, Prodinger WM, Figge MT, Zipfel PF, Skerka C 2016 Complement factor H related protein 3 (FHR3) blocks C3d-mediated co-activation of human B cells. J Immunol 197: 620-9 PubMed
Berges C, Kerkau T, Werner S, Wolf N, Winter N, Hünig T, Einsele H, Topp MS, Beyersdorf N 2016

Hsp90 inhibition ameliorates CD4+ T cell-mediated acute Graft versus Host Disease in mice.

Immun Inflamm Dis 4: 463-73

PubMed
Halder LD, Abdelfatah MA, Jo E, Jacobsen ID, Westermann M, Beyersdorf N, Lorkowski S, Zipfel PF, Skerka C 2017 Factor H binds to extracellular DNA traps released from human blood monocytes in response to Candida albicans. Front Immunol 7: 671

PubMed

Klaile E, Müller M, Schäfer MR, Feer S, Heyl K, Stock M, Klassert T, Zipfel P, Singer P 2017 Binding of Candida albicans to human CEACAM1 and CEACAM6 modulates the inflammatory response of intestinal epithelial cells. mBio 8(2) pii: e02142-16 PubMed
Bergfeld A, Dasari P, Werner S, Hughes TR, Song WC, Hortschansky P, Brakhage AA, Hünig T, Zipfel PF, Beyersdorf N 2017 Direct binding of the pH-regulated protein 1 (Pra1) from Candida albicans inhibits cytokine secretion by mouse CD4+ T cells.

Front Microbiol 8: 844

Front Microbil