Proinflammatory response of immature human dendritic cells is mediated by dectin-1 after exposure to Aspergillus fumigatus germ tubes.
BACKGROUND
Invasive fungal infections caused by Aspergillus fumigatus represent a great challenge for immunocompromised patients. Pathogen detection is mediated by different receptors, including Toll-like receptors (TLRs), C-type lectins, and pentraxines. However, little is known about their relevance for immature human dendritic cells (iDCs).


METHODS
The gene expression pattern of iDCs after exposure to A. fumigatus germ tubes was studied by use of whole genome microarray analysis and real-time polymerase chain reaction. Fungal receptors were targeted by means of short interfering RNAs (siRNAs), which were used to knock down expression of TLR2, TLR4, DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin), PTX3 (pentraxin-related gene), dectin-1 (C-type lectin domain family 7, member A), and CARD9 (caspase recruitment domain family, member 9).


RESULTS
Exposure to A. fumigatus induced expression of cytokines, chemokines, costimulatory molecules, and genes involved in prostaglandin synthesis, as well as genes related to fungal recognition and phagocytosis. Silencing of dectin-1 resulted in reduced expression of proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-12), which was also reduced by anti-Dectin-1 antibody treatment prior to exposure to A. fumigatus, zymosan, or Candida albicans.


CONCLUSIONS
Dectin-1 was identified as an important receptor for A. fumigatus and C. albicans on human iDCs and was found to be involved in the induction of a proinflammatory cytokine response.
Mezger
Markus
M
Medizinische Klinik und Poliklinik II, Würzburg, Germany.
Kneitz
Susanne
S
Wozniok
Iwona
I
Kurzai
Oliver
O
Einsele
Hermann
H
Loeffler
Juergen
J
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001228:Aspergillosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D037181:Lectins, C-Type; D008565:Membrane Proteins / Q000276:immunology*; D009419:Nerve Tissue Proteins / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D000099181:Dectin-1
D000911:Antibodies, Monoclonal; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; D000099181:Dectin-1