Interaction analyses of human monocytes co-cultured with different forms of Aspergillus fumigatus.
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-alpha (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.
Loeffler
Juergen
J
Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany.
Haddad
Ziad
Z
Department of Hematology and Oncology, Tübingen University Hospital, Tübingen, Germany.
Bonin
Michael
M
Interdisciplinary Centre for Clinical Research (IZKF) Microarray Facility, University of Tübingen, Tübingen, Germany.
Romeike
Nele
N
Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany.
Mezger
Markus
M
Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany.
Schumacher
Ulrike
U
Institute for Medical Microbiology, Tübingen University Hospital, Tübingen, Germany.
Kapp
Markus
M
Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany.
Gebhardt
Florian
F
Department of Hematology and Oncology, Tübingen University Hospital, Tübingen, Germany.
Grigoleit
Goetz-Ulrich
GU
Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany.
Stevanović
Stefan
S
Department of Immunology, Institute for Cell Biology, University of Tübingen, Tübingen, Germany.
Einsele
Hermann
H
Department of Hematology and Oncology, Medizinische Klinik II, University of Würzburg, Würzburg, Germany.
Hebart
Holger
H
Staufer-Klinik, Innere Medizin, Schwäbisch Gmünd, Germany.
D001232:Aspergillus fumigatus / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D054884:Host-Pathogen Interactions; D006801:Humans; D025301:Hyphae / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000502:physiology*; D015849:Plasminogen Inactivators / Q000235:genetics / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D013172:Spores, Fungal / Q000502:physiology; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
D016209:Interleukin-8; D015849:Plasminogen Inactivators; D055293:Receptors, Urokinase Plasminogen Activator; D018799:Intercellular Adhesion Molecule-1; D014568:Urokinase-Type Plasminogen Activator