Genome wide expression profiling reveals suppression of host defence responses during colonisation by Neisseria meningitides but not N. lactamica.
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.
Infectious Diseases, Genome Institute of Singapore, Singapore, Singapore.
Hazel En En
HE
Wong
Ming-Shi
MS
Li
J Simon
JS
Kroll
Martin L
ML
Hibberd
Paul R
PR
Langford
D000222:Adaptation, Physiological; D001426:Bacterial Proteins / Q000378:metabolism; D001980:Bronchi / Q000166:cytology; D002460:Cell Line; D003173:Complement C1s / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000382:microbiology; D015536:Down-Regulation; D004734:Energy Metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D005786:Gene Expression Regulation / Q000276:immunology; D023281:Genomics; D006801:Humans; D007109:Immunity / Q000235:genetics*; D018836:Inflammation Mediators / Q000378:metabolism; D050296:Microbial Viability; D042806:Neisseria lactamica / Q000378:metabolism / Q000502:physiology*; D009345:Neisseria meningitidis / Q000378:metabolism / Q000502:physiology*; D013045:Species Specificity; D013997:Time Factors; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001426:Bacterial Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D003173:Complement C1s