The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro.

Hdl Handle:
http://hdl.handle.net/10147/141070
Title:
The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro.
Authors:
Morton, Charles O; Varga, John J; Hornbach, Anke; Mezger, Markus; Sennefelder, Helga; Kneitz, Susanne; Kurzai, Oliver; Krappmann, Sven; Einsele, Hermann; Nierman, William C; Rogers, Thomas R; Loeffler, Juergen
Affiliation:
Department of Clinical Microbiology, Trinity College Dublin, Dublin, Ireland.
Citation:
The temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. 2011, 6 (1):e16016 PLoS ONE
Journal:
PloS one
Issue Date:
Jan-2011
URI:
http://hdl.handle.net/10147/141070
DOI:
10.1371/journal.pone.0016016
PubMed ID:
21264256
Abstract:
Dendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Monocyte-derived immature DCs (iDC) were infected with viable resting conidia of Aspergillus fumigatus (Af293) for 12 hours at an MOI of 5; cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to microarrays. iDC cell death increased at 6 h in the presence of A. fumigatus which coincided with fungal germ tube emergence; >80% of conidia were associated with iDC. Over the time course A. fumigatus differentially regulated 210 genes, FunCat analysis indicated significant up-regulation of genes involved in fermentation, drug transport, pathogenesis and response to oxidative stress. Genes related to cytotoxicity were differentially regulated but the gliotoxin biosynthesis genes were down regulated over the time course, while Aspf1 was up-regulated at 9 h and 12 h. There was an up-regulation of genes in the subtelomeric regions of the genome as the interaction progressed. The genes up-regulated by iDC in the presence of A. fumigatus indicated that they were producing a pro-inflammatory response which was consistent with previous transcriptome studies of iDC interacting with A. fumigatus germ tubes. This study shows that A. fumigatus adapts to phagocytosis by iDCs by utilising genes that allow it to survive the interaction rather than just up-regulation of specific virulence genes.
Item Type:
Article
Language:
en
MeSH:
Aspergillus fumigatus; Cells, Cultured; Dendritic Cells; Gene Expression Regulation; Host-Pathogen Interactions; Humans; Immune Evasion; Inflammation; Phagocytosis
ISSN:
1932-6203

Full metadata record

DC FieldValue Language
dc.contributor.authorMorton, Charles Oen
dc.contributor.authorVarga, John Jen
dc.contributor.authorHornbach, Ankeen
dc.contributor.authorMezger, Markusen
dc.contributor.authorSennefelder, Helgaen
dc.contributor.authorKneitz, Susanneen
dc.contributor.authorKurzai, Oliveren
dc.contributor.authorKrappmann, Svenen
dc.contributor.authorEinsele, Hermannen
dc.contributor.authorNierman, William Cen
dc.contributor.authorRogers, Thomas Ren
dc.contributor.authorLoeffler, Juergenen
dc.date.accessioned2011-08-29T10:18:47Z-
dc.date.available2011-08-29T10:18:47Z-
dc.date.issued2011-01-
dc.identifier.citationThe temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro. 2011, 6 (1):e16016 PLoS ONEen
dc.identifier.issn1932-6203-
dc.identifier.pmid21264256-
dc.identifier.doi10.1371/journal.pone.0016016-
dc.identifier.urihttp://hdl.handle.net/10147/141070-
dc.description.abstractDendritic cells (DC) are the most important antigen presenting cells and play a pivotal role in host immunity to infectious agents by acting as a bridge between the innate and adaptive immune systems. Monocyte-derived immature DCs (iDC) were infected with viable resting conidia of Aspergillus fumigatus (Af293) for 12 hours at an MOI of 5; cells were sampled every three hours. RNA was extracted from both organisms at each time point and hybridised to microarrays. iDC cell death increased at 6 h in the presence of A. fumigatus which coincided with fungal germ tube emergence; >80% of conidia were associated with iDC. Over the time course A. fumigatus differentially regulated 210 genes, FunCat analysis indicated significant up-regulation of genes involved in fermentation, drug transport, pathogenesis and response to oxidative stress. Genes related to cytotoxicity were differentially regulated but the gliotoxin biosynthesis genes were down regulated over the time course, while Aspf1 was up-regulated at 9 h and 12 h. There was an up-regulation of genes in the subtelomeric regions of the genome as the interaction progressed. The genes up-regulated by iDC in the presence of A. fumigatus indicated that they were producing a pro-inflammatory response which was consistent with previous transcriptome studies of iDC interacting with A. fumigatus germ tubes. This study shows that A. fumigatus adapts to phagocytosis by iDCs by utilising genes that allow it to survive the interaction rather than just up-regulation of specific virulence genes.-
dc.language.isoenen
dc.subject.meshAspergillus fumigatus-
dc.subject.meshCells, Cultured-
dc.subject.meshDendritic Cells-
dc.subject.meshGene Expression Regulation-
dc.subject.meshHost-Pathogen Interactions-
dc.subject.meshHumans-
dc.subject.meshImmune Evasion-
dc.subject.meshInflammation-
dc.subject.meshPhagocytosis-
dc.titleThe temporal dynamics of differential gene expression in Aspergillus fumigatus interacting with human immature dendritic cells in vitro.en
dc.typeArticleen
dc.contributor.departmentDepartment of Clinical Microbiology, Trinity College Dublin, Dublin, Ireland.en
dc.identifier.journalPloS oneen

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