Secreted fungal proteins in immune evasion and pathogenicity
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.
PD Dr. Niklas Beyersdorf
Institute for Virology and Immunobiology and Research Center for Infectious Diseases (ZINF)
Julius Maximilians University Würzburg
Prof. Dr. Peter F. Zipfel
Department of Infection Biology
Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute
Dühring S, Germerodt S, Skerka C, Zipfel PF, Dandekar T, Schuster S
Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies.
Front Microbiol 6: 625
|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
|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
|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|
|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