Divergent responses to peptidoglycans derived from different E. coli serotypes influence inflammatory outcome in trout, Oncorhynchus mykiss, macrophages

Sebastian Boltaña,Frederick Goetz,Davinia Morera,Simon A Mackenzie,Felipe Reyes-Lopez

doi:10.1186/1471-2164-12-34

Sebastian Boltaña, Frederick Goetz + Show 3 more

Open Access

https://doi.org/10.1186/1471-2164-12-34

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Journal: BMC Genomics	Publication Date: Jan 14, 2011
Citations: 81	License type: cc-by

Affiliation: Autonomous University of Barcelona

Abstract

BackgroundPathogen-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.ResultsTranscript 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.ConclusionResponses 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.

Highlights

Pathogen-associated molecular patterns (PAMPs) are structural components of pathogens such as lipopolysaccharide (LPS) and peptidoglycan (PGN) from bacterial cell walls
Our results show that trout macrophages differentially respond to different PGNs at the level of the transcriptome by either differentially activating RNA transcripts related to prostaglandin synthesis resulting in the liberation of prostaglandin’s (PGN-O111:B4) or by generating a non-defined inflammatory response, (PGN-K12)
Gene expression profiles obtained highlighted a marked contrast in the macrophage response to PGN purified from E. coli (PGN-O111:B4 and K12)

Summary

Introduction

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. In Drosophila, PGN recognition is achieved by the Toll or Immune deficiency (Imd) pathways, at least in part, through peptidoglycan recognition proteins (PGRPs) [25,26]. Studies addressing different responses to serotypespecific PGNs are scarce throughout the vertebrata including mammals

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