title: The early phase transcriptome of bovine monocyte-derived macrophages infected with Staphylococcus aureus in vitro.
abstract: BACKGROUND
  In the mammary gland, local recruitment and action of macrophages is a key immunological defence mechanism against infection. Macrophages are members of the innate immune system, serve as the first line of the defence against invading pathogens and are critical effectors and regulators of inflammation. We have examined the early phase response of bovine macrophages to infection with live Staphylococcus aureus. Genome-wide transcript profiling of blood monocyte-derived macrophages from six Norwegian Red heifers infected with live S. aureus for 2 and 6 hours in vitro was performed.
  
  
  RESULTS
  About 420 of the 17 000 genes on the ARK-Genomics bovine cDNA array were differentially regulated at 6 hours post infection. Approximately 70% of the responding genes had a known identity (Entrez Gene ID) and were used in the identification of overrepresented pathways and biological functions in the dataset.Analysis of a subset of differentially regulated genes (List eQG) obtained by comparison with data from genome-wide association mapping in Norwegian Red cattle identified anti-inflammatory cytokines interleukin 4 and interleukin 13 as putative expression quantitative trait loci, suggesting that S. aureus infection triggers alternative activation of macrophages. Moreover, several classical activation pathways were found, mainly cellular immune response and cytokine signaling pathways, i.e. triggering receptor expressed on myeloid cells 1 (TREM1) and nucleotide-binding and oligomerization domain-like receptor (NLR) pathways. Tumor necrosis factor receptor superfamily member 5 (CD40 ligand) was identified as an upstream regulator which points toward CD40 likely acting as a co-stimulatory receptor during Toll-like receptor 2(TLR2)-mediated inflammatory response of bovine macrophages to S. aureus infection. Furthermore, peptidoglycan was identified as an upstream regulator in the List eQG, which indicates that this bacterial cell-wall component might be pivotal in macrophage intracellular bacterial recognition during early inflammation.
  
  
  CONCLUSIONS
  Here we have shown that in vitro infection of bovine macrophages with live S. aureus induced both alternative and classical activation pathways. Alternative activation of macrophages may be a mechanism contributing to intracellular persistence of S. aureus in the course of inflammation such as during mastitis in dairy cattle.
authors.forename: Anna Monika
authors.initials: AM
authors.lastname: Lewandowska-Sabat
authors.forename: Guro Margrethe
authors.initials: GM
authors.lastname: Boman
authors.forename: Alison
authors.initials: A
authors.lastname: Downing
authors.forename: Richard
authors.initials: R
authors.lastname: Talbot
authors.forename: Anne Kristine
authors.initials: AK
authors.lastname: Storset
authors.affiliation: Department of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, P,O, Box 8146 Dep, NO-0033 Oslo, Norway. ingrid.olsaker@nvh.no.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Olsaker
mesh_terms: D000818:Animals; D002417:Cattle; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008264:Macrophages / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D058977:Molecular Sequence Annotation; D015203:Reproducibility of Results; D015398:Signal Transduction; D013203:Staphylococcal Infections / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D059467:Transcriptome