Project C4

Modulation of monocytes and B cell functions by humoral immunity in response to Candida albicans

Protection from C. albicans infection is mainly based on innate cellular immunity that is fine-tuned by T cells. Project C4 aims at elucidating how C. albicans changes the humoral immune response to affect the cellular response, Monocytes/macrophages are an essential part of antifungal immunity, in part due to their regulatory role at the intersection of innate and adaptive immune responses. In the first funding period we characterized the reaction of monocytes to C. albicans and found that monocytes release extracellular DNA nets (ETs) that trap the fungal cells in a manner similar to neutrophilic granulocytes. These ETs contain substances like citrullinated histones and myeolperoxidase that attack the fungus. C. albicans is known to recruit human regulators like complement factor H to the surface to inhibit innate immune reactions like complement activation and opsonization. Recently we identified kallikrein, which is activated from prekallikrein in response to contact activation on the C. albicans surface as a complement activator that cleaves C3 and factor B. However, factor H on C. albicans also inhibits this pathway of complement activation. Further studies will include the detailed analysis of fungal proteins and recruited human complement regulatory proteins (FHR1) and their interaction with monocytes and B cells via distinct receptors. Furthermore, the analysis of B cell populations reacting to C. albicans in reporter mice infected or colonized with C. albicans will give insights into the in vivo immune response to C. albicans.

C. albicans (hyphae) trapped in extracellular nets derived from monocytes.
C. albicans (hyphae) trapped in extracellular nets derived from monocytes.
Principal Investigators
Prof. Dr. Berit Jungnickel
Prof. Dr. Berit Jungnickel

Center for Molecular Biomedicine

Institute of Biochemistry and Biophysics

 

Friedrich Schiller University Jena

berit.jungnickel@uni-jena.de

Prof. 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
Meinel C, Spartà G, Dahse H-M, Hörhold F, König R, Westermann M, Cseresnyés Z, Coldewey SM, Figge MT, Hammerschmidt S, Skerka C, Zipfel PF 2018 Streptococcus pneumoniae from patients with hemolytic uremic syndrome binds human plasminogen via the surface protein PspC and uses plasmin to damage human endothelial cells. J Infect Dis 217: 358-70 PubMed
Irmscher S, Döring N, Halder LD, Jo EAH, Kopka I, Dunker C, Jacobsen ID, Luo S, Slevogt H, Lorkowski S, Beyersdorf N, Zipfel PF, Skerka C 2018 Kallikrein cleaves C3 and activates complement. J Innate Immun 10: 94-105 PubMed
Hummert S, Glock C, Lang SN, Hummert C, Skerka C, Zipfel PF, Germerodt S, Schuster S 2018 Playing ’hide-and-seek’ with factor H: game-theoretical analysis of a single nucleotide polymorphism. J R Soc Interface 15: 20170963 Royal Society Publishing
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
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
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
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
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
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