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.
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
PD Dr. Matthias Brock
Institute of Microbiology
Friedrich Schiller University Jena
Research Group Microbial Biochemistry and Physiology
Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute
Dr. Katrin G. Heinze
Research Group Biophotonics
Rudolf Virchow Center & Bio-Imaging Center
Julius Maximilians University Würzburg
Jacobsen ID, Lüttich A, Kurzai O, Hube B, Brock M
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
|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
|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