title: Divergent responses to peptidoglycans derived from different E. coli serotypes influence inflammatory outcome in trout, Oncorhynchus mykiss, macrophages.
abstract: BACKGROUND
  Pathogen-associated molecular patterns (PAMPs) are structural components of pathogens such as lipopolysaccharide (LPS) and peptidoglycan (PGN) from bacterial cell walls. PAMP-recognition by the host results in an induction of defence-related genes and often the generation of an inflammatory response. We evaluated both the transcriptomic and inflammatory response in trout (O. mykiss) macrophages in primary cell culture stimulated with DAP-PGN (DAP; meso-diaminopimelic acid, PGN; peptidoglycan) from two strains of Escherichia coli (PGN-K12 and PGN-O111:B4) over time.
  
  
  RESULTS
  Transcript profiling was assessed using function-targeted cDNA microarray hybridisation (n = 36) and results show differential responses to both PGNs that are both time and treatment dependent. Wild type E. coli (K12) generated an increase in transcript number/diversity over time whereas PGN-O111:B4 stimulation resulted in a more specific and intense response. In line with this, Gene Ontology analysis (GO) highlights a specific transcriptomic remodelling for PGN-O111:B4 whereas results obtained for PGN-K12 show a high similarity to a generalised inflammatory priming response where multiple functional classes are related to ribosome biogenesis or cellular metabolism. Prostaglandin release was induced by both PGNs and macrophages were significantly more sensitive to PGN-O111:B4 as suggested from microarray data.
  
  
  CONCLUSIONS
  Responses at the level of the transcriptome and the inflammatory outcome (prostaglandin synthesis) highlight the different sensitivity of the macrophage to slight differences (serotype) in peptidoglycan structure. Such divergent responses are likely to involve differential receptor sensitivity to ligands or indeed different receptor types. Such changes in biological response will likely reflect upon pathogenicity of certain serotypes and the development of disease.
authors.affiliation: Institute of Biotechnology and Biomedicine, Universitat Autónoma de Barcelona, 08193 Barcelona, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Boltaña
authors.forename: Felipe
authors.initials: F
authors.lastname: Reyes-Lopez
authors.forename: Davinia
authors.initials: D
authors.lastname: Morera
authors.forename: Frederick
authors.initials: F
authors.lastname: Goetz
authors.forename: Simon A
authors.initials: SA
authors.lastname: MacKenzie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003960:Diaminopimelic Acid / Q000378:metabolism / Q000494:pharmacology*; D004926:Escherichia coli / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017686:Oncorhynchus mykiss / Q000276:immunology*; D010457:Peptidoglycan / Q000378:metabolism / Q000494:pharmacology*; D016133:Polymerase Chain Reaction
chemical_list: D010457:Peptidoglycan; D003960:Diaminopimelic Acid