Project A3

Project Description

Pulmonary A. fumigatus infection (A. fumigatus in red), Beilhack lab 2013
Pulmonary A. fumigatus infection (A. fumigatus in red), Beilhack lab 2013

In vivo analysis of temporal and spatial disease progression and immune cell recruitment during invasive Aspergillus fumigatus and Candida albicans infection 

Aspergillus fumigatus and Candida albicans cause life-threatening fungal infections. While A. fumigatus is the major cause of invasive pulmonary aspergillosis in immunompromised patients, C. albicans is a common commensal of humans, but can turn into a pathogen as a consequence of barrier disruption or imbalances of the immune system. Despite differences in the early onset of infection, clearance of infections depends on immune effector cells from the innate immune system. Until now, only limited information is available concerning the time-resolved progression and spatial distribution of both fungal species during infection in dependence of the underlying predisposing condition. Furthermore, the dynamics of immune cell recruitment and the way in which they act in concert is hardly understood. This project employs various in vivo and ex vivo imaging techniques to visualise disease progression, immune cell recruitment and the physical interactions among immune cells and with the pathogen under in vivo conditions. By modulating the immune system we will analyse the changes in interaction patterns and its effect on the outcome of fungal infections. While a primary focus is given to A. fumigatus lung infections, systemic infections will be performed for comparative analyses between A. fumigatus and C. albicans infections. Here, we will focus on the dynamics of immune cells in infected tissues and analyse fungal species-specific differences. By these analyses we aim to elucidate the interplay of host and pathogen under in vivo conditions.

Principal Investigators

Prof. Dr. Andreas Beilhack
Prof. Dr. Andreas Beilhack

Faculty of Medicine, Department of Internal Medicine II, Center for Experimental Molecular Medicine, Experimental Stem Cell Transplantation and Research Center for Infectious Diseases (ZINF)  

Julius Maximilians University Würzburg

beilhack_a@medizin.uni-wuerzburg.de

Prof. Dr. Katrin G. Heinze
Prof. Dr. Katrin G. Heinze

Research Group Biophotonics

Rudolf Virchow Center & Bio-Imaging Center  

Julius Maximilians University Würzburg

katrin.heinze@virchow.uni-wuerzburg.de

Dr. Ulrich Terpitz
Dr. Ulrich Terpitz

Biocenter, Department of Biotechnology and Biophysics 

Julius Maximilians University Würzburg

ulrich.terpitz@uni-wuerzburg.de

Publications

Author Year Title Journal Links

Jacobsen ID, Lüttich A, Kurzai O, Hube B, Brock M

2014

In vivo imaging of disseminated murine Candida albicans infection reveals unexpected host sites of fungal persistence during antifungal therapy.

J Antimicrob Chemother 69: 2785-96

PubMed
Ramachandra S, Linde J, Brock M, Guthke R, Hube B, Brunke S 2014

Regulatory networks controlling nitrogen sensing and uptake in Candida albicans.

PLoS One 9: e92734 PubMed
Rieber N, Singh A, Carevic M, Öz H, Bouzani M, Amich J, Ost M, Ye Z, Ballbach M, Schäfer I, Mezger M, Klimosch SN, Weber ANR, Handgretinger R, Krappmann S, Liese J, Engeholm M, Schüle R, Salish HR, Marodi L, Speckmann C, Grimbacher B, Ruland J, Brown GD, Beilhack A, Loeffler J, Hartl D 2015 Pathogenic fungi regulate T-cell immunity by inducing neutrophilic myeloid-derived suppressor cells through a Dectin-1/CARD9 and ROS-mediated mechanism. Cell Host Microbe 17: 507-14 PubMed
Kalleda N, Amich J, Arslan B, Poreddy S, Mattenheimer K, Mokhtari Z, Einsele H, Brock M, Heinze K, Beilhack A 2016 Dynamic immune cell recruitment after murine pulmonary Aspergillus fumigatus infection under different immunosuppressive regimens. Front Microbiol 7: 1107 PubMed
Lother J, Breitschopf T, Krappmann S, Morton CO, Bouzani M, Kurzai O, Gunzer M, Hasenberg M, Einsele H, Loeffler J 2014 Human dendritic cell subsets display distinct interactions with the mould Aspergillus fumigatus. Int J Med Microbiol 304: 1160-8 PubMed
Savers A, Rasid O, Parlato M, Brock M, Jouvion G, Ryffel B, Cavaillon JM, Eberl G, Ibrahim-Granet O 2016 Infection-mediated priming of phagocytes protects against lethal secondary Aspergillus fumigatus challenge. PLoS One 11: e0153829 PubMed
Dietl AM, Amich J, Leal S, Beckmann N, Binder U, Beilhack A, Pearlman E, Haas H 2016

Histidine biosynthesis plays a crucial role in metal homeostasis and virulence of Aspergillus fumigatus.

Virulence 7: 465-76

PubMed
Chopra M, Biehl M, Steinfatt T, Brandl A, Kums J, Amich J, Vaeth M, Kuen J, Holtappels R, Podlech J, Mottok A, Kraus S, Jordán Garrote AL, Bäuerlein CA, Brede C, Ribecchini E, Fick A, Seher A, Polz J, Ottmüller K, Baker J, Nishikii H, Ritz M, Mattenheimer K, Schwinn S, Winter T, Schäfer V, Krappmann S, Einsele H, Mueller TD, Reddehase MJ, Lutz MB, Männel DN, Berberich-Siebelt F, Wajant H, Beilhack A 2016 Exogenous TNFR2 activation protects from acute GvHD by induction of host Treg expansion.

J Exp Med 213: 1881-900

PubMed