IFN-γ amplifies NFκB-dependent Neisseria meningitides invasion of epithelial cells via specific upregulation of CEA-related cell adhesion molecule 1

NJE Griffiths, CJ Bradley, RS Heyderman, M Virji

Research output: Contribution to journalArticle (Academic Journal)peer-review

39 Citations (Scopus)

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.
Translated title of the contributionIFN-γ amplifies NFκB-dependent Neisseria meningitides invasion of epithelial cells via specific upregulation of CEA-related cell adhesion molecule 1
Original languageEnglish
Pages (from-to)2968 - 2983
Number of pages16
JournalCellular Microbiology
Volume9 (12)
DOIs
Publication statusPublished - Dec 2007

Bibliographical note

Publisher: Blackwell

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