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Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus

Juergen Loeffler^1,, Ziad Haddad^2,, Michael Bonin³, Nele Romeike¹, Markus Mezger¹, Ulrike Schumacher⁴, Markus Kapp¹, Florian Gebhardt², Goetz-Ulrich Grigoleit¹, Stefan Stevanovi⁵, Hermann Einsele¹ and Holger Hebart⁶

¹ Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany

² Department of Hematology and Oncology, Tübingen University Hospital, Tübingen, Germany

³ Interdisciplinary Centre for Clinical Research (IZKF) Microarray Facility, University of Tübingen, Tübingen, Germany

⁴ Institute for Medical Microbiology, Tübingen University Hospital, Tübingen, Germany

⁵ Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany

⁶ Staufer-Klinik, Innere Medizin, Schwäbisch Gmünd, Germany

Correspondence
Juergen Loeffler
loeffler_j{at}klinik.uni-wuerzburg.de

Received May 8, 2008
Accepted September 18, 2008

Monocytes play a major role in the cellular defence against Aspergillus fumigatus in immunocompromised patients. To obtain a better understanding of the mechanisms involved in this interaction, phagocytosis and gene expression profiling of human monocytes was carried out after incubation with A. fumigatus resting, swollen and germinating conidia and hyphae (for 3, 6 and 9 h). The majority of monocytes phagocytosed up to three conidia during the first 3 h of incubation. Microarray analysis showed an increased expression level of immune-relevant genes, which was dependent on the germination state of the fungus and the incubation period. Among these genes, those encoding interleukin-8, macrophage inflammatory protein 3- (CCL20) and monocyte chemotactic protein-1 (CCL2) were found to be potential key regulators involved in the A. fumigatus-induced immune response. In addition, A. fumigatus was found to be an inducer of the genes encoding urokinase type plasminogen activator (uPA), urokinase type plasminogen activator receptor (uPAR),plasminogen activator inhibitor (PAI), pentraxin-3 (PTX3) and intercellular adhesion molecule-1 (ICAM-1), which, in combination, may contribute to thrombosis and local lung tissue injury.

Abbreviations: IA, invasive aspergillosis; IL, interleukin; SLR, signal log₂ ratio; TLR, Toll-like receptor; TNF, tumour necrosis factor.

These authors contributed equally to this work.