Gene expression profiling of dendritic cells reveals important mechanisms associated with predisposition to Staphylococcus infections.

TitleGene expression profiling of dendritic cells reveals important mechanisms associated with predisposition to Staphylococcus infections.
Publication TypeJournal Article
Year of Publication2011
AuthorsToufeer, M, Bonnefont, CMD, Foulon, E, Caubet, C, Tasca, C, Aurel, M-R, Robert-Granié, C, Rupp, R, Foucras, G
JournalPLoS One
Volume6
Issue8
Paginatione22147
Date Published2011
ISSN1932-6203
KeywordsAnimals, Bone Marrow Cells, Cells, Cultured, Dendritic Cells, Disease Resistance, Female, Gene Expression Profiling, Genetic Predisposition to Disease, Host-Pathogen Interactions, Hot Temperature, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Sheep, Staphylococcal Infections, Staphylococcus aureus, Transcriptome, Vaccines, Attenuated
Abstract

BACKGROUND: Staphylococcus aureus is a major pathogen of humans and animals and emerging antibiotic-resistant strains have further increased the concern of this health issue. Host genetics influence susceptibility to S. aureus infections, and the genes determining the outcome of infections should be identified to find alternative therapies to treatment with antibiotics. Here, we used outbred animals from a divergent selection based on susceptibility towards Staphylococcus infection to explore host immunogenetics.METHODOLOGY/PRINCIPAL FINDINGS: We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals showing different degrees of susceptibility had distinct gene expression profiles. We measured gene expression levels of in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hrs) by using 15 k ovine Agilent microarrays. Furthermore, differential expression of a selected number of genes was confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and showed that genes involved in the inflammatory process and T helper cell polarization were highly up-regulated upon stimulation. Moreover, a set of 204 genes were statistically differentially expressed between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, over-expression of the C1q and Ido1 genes was observed in the resistant line and suggested a role of classical pathway of complement and early regulation of inflammation pathways, respectively. On the contrary, over expression of genes involved in the IL1R pathway was observed in susceptible animals. Furthermore, the leucocyte extravasation pathway was also found to be dominant in the susceptible line.CONCLUSION/SIGNIFICANCE: We successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in an 8-hour kinetics experiment. The distinct transcriptional profiles of dendritic cells obtained from resistant and susceptible animals may explain susceptibility towards S. aureus infections in a broader context.

DOI10.1371/journal.pone.0022147
Alternate JournalPLoS ONE
PubMed ID21857913
PubMed Central IDPMC3155527