title: Co-Transcriptomes of Initial Interactions In Vitro between Streptococcus Pneumoniae and Human Pleural Mesothelial Cells.
abstract: Streptococcus pneumoniae (Spn) is a major causative organism of empyema, an inflammatory condition occurring in the pleural sac. In this study, we used human and Spn cDNA microarrays to characterize the transcriptional responses occurring during initial contact between Spn and a human pleural mesothelial cell line (PMC) in vitro. Using stringent filtering criteria, 42 and 23 Spn genes were up-and down-regulated respectively. In particular, genes encoding factors potentially involved in metabolic processes and Spn adherence to eukaryotic cells were up-regulated e.g. glnQ, glnA, aliA, psaB, lytB and nox. After Spn initial contact, 870 human genes were differentially regulated and the largest numbers of significant gene expression changes were found in canonical pathways for eukaryotic initiation factor 2 signaling (60 genes out of 171), oxidative phosphorylation (32/103), mitochondrial dysfunction (37/164), eIF4 and p70S6K signaling (28/142), mTOR signaling (27/182), NRF2-mediated oxidative stress response (20/177), epithelial adherens junction remodeling (11/66) and ubiquitination (22/254). The cellular response appeared to be directed towards host cell survival and defense. Spn did not activate NF-kB or phosphorylate p38 MAPK or induce cytokine production from PMC. Moreover, Spn infection of TNF-α pre-stimulated PMC inhibited production of IL-6 and IL-8 secretion by >50% (p<0.01). In summary, this descriptive study provides datasets and a platform for examining further the molecular mechanisms underlying the pathogenesis of empyema.
authors.affiliation: Neisseria Research Group, Molecular Microbiology, Clinical and Experimental Sciences, Sir Henry Wellcome laboratories, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Heath
authors.affiliation: Neisseria Research Group, Molecular Microbiology, Clinical and Experimental Sciences, Sir Henry Wellcome laboratories, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Maria
authors.initials: M
authors.lastname: del Mar Cendra
authors.affiliation: Neisseria Research Group, Molecular Microbiology, Clinical and Experimental Sciences, Sir Henry Wellcome laboratories, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Alastair
authors.initials: A
authors.lastname: Watson
authors.affiliation: Department of Pathology and Microbiology, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC, Canada.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Auger
authors.affiliation: Neisseria Research Group, Molecular Microbiology, Clinical and Experimental Sciences, Sir Henry Wellcome laboratories, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Anish
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Queen's Medical Centre, Nottingham, NG7 2UH, United Kingdom.
authors.forename: Paddy
authors.initials: P
authors.lastname: Tighe
authors.affiliation: Neisseria Research Group, Molecular Microbiology, Clinical and Experimental Sciences, Sir Henry Wellcome laboratories, University of Southampton Faculty of Medicine, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: Myron
authors.initials: M
authors.lastname: Christodoulides
mesh_terms: D000465:Algorithms; D002448:Cell Adhesion; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004653:Empyema / Q000382:microbiology*; D004847:Epithelial Cells / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism* / Q000382:microbiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011008:Pneumococcal Infections / Q000235:genetics / Q000382:microbiology*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000235:genetics*; D059467:Transcriptome; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016207:Cytokines; D018076:DNA, Complementary; D012333:RNA, Messenger; D048051:p38 Mitogen-Activated Protein Kinases