Abstract
Both Neisseria meningitidis and the closely related bacterium Neisseria lactamica colonise human nasopharyngeal mucosal surface, but only N. meningitidis invades the bloodstream to cause potentially life-threatening meningitis and septicaemia. We have hypothesised that the two neisserial species differentially modulate host respiratory epithelial cell gene expression reflecting their disease potential. Confluent monolayers of 16HBE14 human bronchial epithelial cells were exposed to live and/or dead N. meningitidis (including capsule and pili mutants) and N. lactamica, and their transcriptomes were compared using whole genome microarrays. Changes in expression of selected genes were subsequently validated using Q-RT-PCR and ELISAs. Live N. meningitidis and N. lactamica induced genes involved in host energy production processes suggesting that both bacterial species utilise host resources. N. meningitidis infection was associated with down-regulation of host defence genes. N. lactamica, relative to N. meningitidis, initiates up-regulation of proinflammatory genes. Bacterial secreted proteins alone induced some of the changes observed. The results suggest N. meningitidis and N. lactamica differentially regulate host respiratory epithelial cell gene expression through colonisation and/or protein secretion, and that this may contribute to subsequent clinical outcomes associated with these bacteria.
Highlights
Neisseria meningitidis and Neisseria lactamica are commensal bacteria that colonise the mucosal surface of the human nasopharynx
These allowed the extent of interaction of wild type (WT) N. lactamica and N. meningitidis, as well as N. meningitidis cap- and pilE- mutants with confluent monolayers of 16HBE14 human respiratory bronchial epithelial cells to be determined
There were no significant differences in association with epithelial cells between WT N. lactamica and N. meningitidis at 3 and 5 hours
Summary
Neisseria meningitidis and Neisseria lactamica are commensal bacteria that colonise the mucosal surface of the human nasopharynx. Colonisation by N. meningitidis involves the adherence of host epithelial cells, which is mediated by components such as the pili [6]. Mutation of the meningococcal pilE gene, encoding the major pilin subunit, results in greatly reduced adherence of bacteria to endothelial and epithelial cells [12]. It is not known whether an equivalent mutation in N. lactamica would have similar effects. A recent review by Schubert-Unkmeir et al [13] outlines the various human gene expression studies that have been done so far using cell lines other than those representing the respiratory tract in response to N. meningitidis. Bonnah et al [14] showed that the mRNA expression of several host genes involved in iron homeostasis were altered upon infection with meningococci, while Plant et al [15] showed that there was an induction of chemokine receptors and cytokines such as CXCR-4, CXCR-5, IL1A, IL1B, IL18 and IFN-c , with most of the host genes induced early in infection
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