title: IFN-gamma amplifies NFkappaB-dependent Neisseria meningitidis invasion of epithelial cells via specific upregulation of CEA-related cell adhesion molecule 1.
abstract: Temporal relationship between viral and bacterial infections has been observed, and may arise via the action of virus-induced inflammatory cytokines. These, by upregulating epithelial receptors targeted by bacteria, may encourage greater bacterial infiltration. In this study, human epithelial cells exposed to interferon-gamma but not tumour necrosis factor-alpha or interleukin 1-beta supported increased meningococcal adhesion and invasion. The increase was related to Opa but not Opc or pili adhesin expression. De novo synthesis of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), a major Opa receptor, occurred in epithelial cells exposed to the cytokine, or when infected with Opa-expressing bacteria. Cell line-dependent differences in invasion that were observed could be correlated with CEACAM expression levels. There was also evidence for Opa/pili synergism leading to high levels of monolayer infiltration by capsulate bacteria. The use of nuclear factor-kappa B (NFkappaB) inhibitors, diferuloylmethane (curcumin) and SN50, abrogated bacterial infiltration of both untreated and interferon-gamma-treated cells. The studies demonstrate the importance of CEACAMs as mediators of increased cellular invasion under conditions of inflammation and bring to light the potential role of NFkappaB pathway in Opa-mediated invasion by meningococci. The data imply that cell-surface remodelling by virally induced cytokines could be one factor that increases host susceptibility to bacterial infection.
authors.affiliation: Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK.
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Griffiths
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Bradley
authors.forename: Robert S
authors.initials: RS
authors.lastname: Heyderman
authors.forename: Mumtaz
authors.initials: M
authors.lastname: Virji
mesh_terms: D018829:Adhesins, Bacterial / Q000502:physiology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis*; D001422:Bacterial Adhesion; D001425:Bacterial Outer Membrane Proteins / Q000502:physiology; D002352:Carrier Proteins / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology; D004847:Epithelial Cells / Q000382:microbiology*; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology*; D016328:NF-kappa B / Q000502:physiology*; D009345:Neisseria meningitidis / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015854:Up-Regulation; D014777:Virus Diseases / Q000276:immunology
chemical_list: D018829:Adhesins, Bacterial; D000894:Anti-Inflammatory Agents, Non-Steroidal; D015703:Antigens, CD; D001425:Bacterial Outer Membrane Proteins; C069847:CD66 antigens; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D016328:NF-kappa B; D010446:Peptide Fragments; D010455:Peptides; C118258:SN50 peptide; C526362:rD-7 peptide; C074517:opc protein, bacteria; C090348:Opa protein, Neisseria; D007371:Interferon-gamma; D003474:Curcumin