Project C4

Project Description

The human pathogenic yeast Candida albicans (C. albicans) responds to the aggressive immune attack of the human host and has consequently developed a multitude of different immune evasion strategies, which are only partly understood. C. albicans responds, controls and inhibits host innate as well as adaptive immune reactions. This project aims at elucidating the mechanisms of adhesion of C. albicans to immune cells as well as immune responses of the host effector cells with special emphasis on monocytes and macrophages. In particular the importance of specific microbial components will be defined and studied that modulate the interaction. Microbial proteins that modulate complement activation are of special interest, as complement cleavage products are the natural ligands of human complement receptors CR3 and CR4 expressed on human monocytes and macrophages. Similarly, C. albicans recruits human plasma proteins such as factor H, or beta(2) glycoprotein 1 (b2GPI) to the surface to restrict complement activation on the surface. With generated microbial proteins and recruited human regulators C. albicans likely influences receptor functions in combination with complement. Analyses in this project will connect human innate immune reactions via complement activation with the subsequent immune responses by human effector cells, predominantly monocytes and macrophages. Furthermore, novel C. albicans surface proteins or molecular structures will be defined that alone or together with human proteins such as b2GPI modulate the immune response. The characterisation of the molecular and the cellular interplay, on the level of single molecules and cells, will be carried out and developed into a bioinformatics-based infection model integrating the knowledge of the ‘game theory’.

Principal Investigators

Prof. Dr. Stefan Lorkowski
Prof. Dr. Stefan Lorkowski

Institute of Nutrition, Department Nutritional Biochemistry

Friedrich-Schiller-University Jena

stefan.lorkowski@uni-jena.de

PD Dr. Christine Skerka
Prof. Dr. Christine Skerka

Department of Infection Biology

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

christine.skerka@leibniz-hki.de

Publications

Author Year Title Journal Links
Kraibooj K, Park HR, Dahse HM, Skerka C, Voigt K, Figge MT 2014 Virulent strain of Lichtheimia corymbifera shows increased phagocytosis by macrophages as revealed by automated microscopy image analysis. Mycoses 57 Suppl 3: 56-66 PubMed

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
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
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

Klassert TE, Bräuer J, Hölzer M, Stock M, Riege K, Zubiría-Barrera C, Müller MM, Rummler S, Skerka C, Marz M, Slevogt H 2017 Differential effects of Vitamins A and D on the transcriptional landscape of human monocytes during Infection. Sci Rep 7: 40599 PubMed